The Wistar Institute Melanoma Research Centre

Wistar Institute
3601 Spruce Street, Room 472
Philadelphia, PA 19104
Information: Jessica L. Kohn, jkohn@wistar.org
215-495-6883

Group Leader

Dr Meenhard Herlyn
Caspar Wistar Professor in Melanoma Research
Director, The Wistar Institute Melanoma Research Centre
Professor, Molecular and Cellular Oncogenesis Program
meenhard-2016

Group Members

Dr. Mizuho Kalabis, Research Assistant Professor
Dr. Clemens Krepler, Research Assistant Professor
Dr. Shyam Somasundaram, Research Assistant Professor
Dr. Gao Zhang, Staff Scientist
Dr. Jianglan Liu, Associate Staff Scientist
Trish Brafford, Wistar Research Assistant
Dr. Ling Li, Wistar Research Assistant
Katrin Sproesser, Wistar Research Assistant
Marilda Beqiri, Research Assistant III
Josh Wang, Research Assistant II
Min Xiao, Research Assistant IV
Brian Gavin, Technician II
Jessica L. Kohn, Laboratory Coordinator

Research

Dr. Meenhard Herlyn’s laboratory at The Wistar Institute focuses on the biology that underlies melanoma, the most aggressive form of skin cancer. His efforts have pioneered the use of the three-dimensional “artificial skin” cultures to study the behavior of both tumor and normal cells that sustain tumor growth, a system known as the tumor microenvironment. The Herlyn Laboratory has transformed the scientific understanding of stem cells as they relate to cancer, and their work on the networks of signaling pathways in melanoma has formed the basis of numerous therapies now in clinical trials or very recently approved.

The ability to model the microenvironment of normal and diseased human tissue through 3-D artificial skin provides the Herlyn Laboratory with a unique insight into cancer research. Growing cells in these tissue-like models induces major changes in gene expression similar to those in animals and patients, making them superbly suited for studies of signaling between normal and malignant cells, tumor formation, and drug resistance. These models also make a unique testing ground for ideas on future therapeutics and drug combinations.

The Herlyn Laboratory also seeks to further define the various signaling pathways that work in cancer cells in order to discover new opportunities to inhibit cancer growth through targeted therapeutics. Since therapy is increasingly guided by the genetic aberrations in tumors, Dr. Herlyn and his colleagues are developing combinations of compounds that take into account the genetic signature of tumors, with the specific goal of individualized cancer therapy. Currently, the Herlyn Laboratory collaborates with pharmaceutical companies as well as academic chemists and structural biologists to select and further develop compounds for tumor inhibition. Tumor heterogeneity, i.e., the differences between cells within one tumor, among different tumor lesions of the same patient, or between patients even if the tumors are of similar genetic signatures, provides major challenges for future therapy. The laboratory is developing biological signatures of melanoma cells that take into account the various forms of heterogeneity.

Another major effort of the Herlyn Laboratory is the study of therapy resistance and tumor dormancy. Tumor cells can become dormant in primary tumors or at any time after metastatic dissemination and can persist in the dormant state for many years, allowing tumors to resist treatment. Dr. Herlyn’s working hypothesis is that defined tumor subpopulations are central to dormancy and drug resistance due to their slow turnover and their non-responsiveness to growth signals. His efforts seek to define how tumor cells escape dormancy for growth, invasion, and metastasis, and how to best develop strategies for therapy.

 

Publications

Shannan B, Chen Q, Watters A, Perego M, Krepler C, Thombre R, Li L, Rajan G, Peterson S, Gimotty PA, Wilson M, Nathanson KL, Gangadhar TC, Schuchter LM, Weeraratna AT, Herlyn M, Vultur A. Enhancing the evaluation of PI3K inhibitors through 3D melanoma models. Pigment Cell Melanoma Res. 2016;29:317-28. PMID26850518 (PMCID4840066)

Krepler C, Xiao M, Sproesser K, Brafford PA, Shannan B, Beqiri M, Liu Q, Xu W, Garman B, Nathanson KL, Xu X, Karakousis GC, Mills GB, Lu Y, Ahmed TA, Poulikakos PI, Caponigro G, Boehm M, Peters M, Schuchter LM, Weeraratna AT, Herlyn M. Personalized preclinical trials in BRAF inhibitor-resistant patient-derived xenograft models identify second-line combination therapies. Clin Cancer Res. 2016;22:1592-602. PMID26673799 (PMCID4818716)

Brafford P, Sproessor K, Krepler C, Herlyn M. 1205Lu is human melanoma depending on the source. J Cancer Sci Ther. 2016;8:113.

Lu H, Liu S, Zhang G, Kwong LN, Zhu Y, Miller JP, Hu Y, Zhong W, Zeng J, Wu L, Krepler C, Sproesser K, Xiao M, Xu W, Karakousis GC, Schuchter LM, Field J, Zhang PJ, Herlyn M, Xu X, Guo W. Oncogenic BRAF-mediated melanoma cell invasion. Cell Rep. 2016;15:2012-24. PMID27210749 (PMCID4889462)

Zhang G, Frederick DT, Wu L, Wei Z, Krepler C, Srinivasan S, Chae YC, Xu X, Choi H, Dimwamwa E, Ope O, Shannan B, Basu D, Zhang D, Guha M, Xiao M, Randell S, Sproesser K, Xu W, Liu J, Karakousis GC, Schuchter LM, Gangadhar TC, Amaravadi RK, Gu M, Xu C, Ghosh A, Xu W, Tian T, Zhang J, Zha S, Liu Q, Brafford P, Weeraratna A, Davies MA, Wargo JA, Avadhani NG, Lu Y, Mills GB, Altieri DC, Flaherty KT, Herlyn M. Targeting mitochondrial biogenesis to overcome drug resistance to MAPK inhibitors. J Clin Invest. 2016;126:1834-56. PMID27043285 (PMCID4855947)

McNeal AS, Liu K, Nakhate V, Natale CA, Duperret EK, Capell BC, Dentchev T, Berger SL, Herlyn M, Seykora JT, Ridky TW. CDKN2B Loss Promotes Progression from Benign Melanocytic Nevus to Melanoma. Cancer Discov. 2015;5(10):1072-85. PMID26183406 PMCID4592422

Wang YJ, Herlyn M. The emerging roles of Oct3 in tumor-initiating cells. Am J Physiol Cell Physiol. 2015;309(11):C709-18. PMID26447206

Krepler C, Xiao M, Spoesser K, Brafford PA, Shannan B, Beqiri M, Liu Q, Xu W, Garman B, Nathanson KL, Xu X, Karakousis GC, Mills GB, Lu Y, Ahmed TA, Poulikakos P, Caponigro G, Boehm M, Peters M, Schuchter LM, Weeraratna AT, Herlyn M. Personalized pre-clinical trials in BRAF inhibitor-resistant patient-derived xenograft models identify second-line combination therapies. Clin Cancer Res. 2015 Dec 16 [Epub ahead of print]. PMID26673799

Ravindran Menon D, Das S, Krepler C, Vultur A, Rinner B, Schauer S, Kashofer K, Wagner K, Zhang G, Bonyadi Rad E, Haass NK, Soyer HP, Gabrielli B, Somasundaram R, Hoefler G, Herlyn M, Schaider H. A stress-induced early innate response casues multidrug tolerance in melanoma. Oncogene. 2015;34(34):4448-59. PMID25417704; PMCIDPMC4442085.

Joshi S, Wels C, Beham-Schmid C, Fukunaga-Kalabis M, Holmen SL, Otte M, Herlyn M, Waldhoer M, Schaider H. Gα13 mediates human cytomegalovirus-encoded chemokine receptor US28-induced cell death in melanoma. Int J Cancer. 2015;137:1503-8. PMID25754407, PMC4496263

Cierlitza M, Chauvistre H, Bogeski I, Zhang X, Hauschild A, Herlyn M, Schadendorf D, Vogt T, Roesch A. Mitochondiral oxidative stress as a novel therapeutic target to overcome intrinsic drug resistance in melanoma subpopulations. Exp Dermatol. 2015;24:155-157. PMID25453510

Kraya AA, Piao S, Xu X, Zhang G, Herlyn M, Gimotty P, Levine B, Amaravadi RK, Speicher DW. Identification of secreted proteins that reflect autophagy dynamics within tumor cells. Autophagy. 2015;11:60-74. PMID25484078

Webster MR, Xu M, Kinzler KA, Kaur A, Appleton J, O’Connell MP, Marchbank K, Valiga A, Dang VM, Perego M, Zhang G, Slipicevic A, Keeney F, Lehrmann E, Wood W 3rd, Becker KG, Kossenov AV, Frederick DT, Flaherty KT, Xu X, Herlyn M, Murphy ME, Weeraratna AT. Wnt5a promotes and adaptive, senescence-like stress stress response, while continuing to drive invasion in melanoma cells. Pigment Cell Melanoma Res. 2015;28:184-195. PMID25407936

Arner E, Daub CO, Vitting-Seerup K, Andersson R, Lilje B, Drablos F, Lennartsson, A, Rönnerblad M, Hrydziuszko O, Vitezic M, Freeman TC, Alhendi A, Arner A, Axton R, Baillie JK, Beckhouse A, Bodega B, Briggs J, Brombacher F, Davis M, Detmar M, Ehrlund A, Endoh M, Eslami A, Fagiolini M, Fairbairn L, Faulkner GJ, Ferrai C, Fisher ME, Forrester L, Goldowitz D, Guler R, Ha T, Hara M, Herlyn M, Ikawa T, Kai C, Kawamoto H, Khachigian L, Klinken PS, Kojima S, Koseki H, Klein S, Mejhert N, Miyaguchi K, Mizuno Y, Morimoto M, Morris KJ, Mummery C, Nakachi Y, Ogishima S, Okada-Hatakeyama M, Okazaki Y, Orlando Y, Ovchinnikov D, Passier R, Patrikakis M, Pombo A, Qin XY, Roy S, Sato H, Savvi S, Saxena A, Schwegmann A, Sugiyama D, Swoboda R, Tanaka R, Tomoiu A, Winteringham LN, Wolvetang E, Yanagi-Mizuochi C, Yoneda M, Zabierowski S, Zhang P, Abugessaisa I, Bertin N, Diehl AD, Fukuda S, Furuno M, Harshbarger J, Hasegawa A, Hori F, Ishikawa-Kato S, Ishizu Y, Itoh M, Kawashima T, Kojima M, Kondo N, Lizio M, Meehan TF, Mungall CJ, Murata M, Nishiyori-Sueki H, Sahin S, Sato-Nagao S, Severin J, de Hoon MJL, Kawai J, Kasukawa T, Lassmann T, Suzuki H, Kawaji H, Summers KM, Wells C, Hume DA, Forrest ARR, Sandelin A, Carninci P, Hayashizaki Y. Gene regulation; transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells. Science. 2015;347:1010-4. PMID25678556

Slipicevic A, Herlyn M. KIT in melanoma: Many shades of grey. J Invest Dermatol. 2015;135:337-8. PMID25573046

Wang T, Xiao M, Ge Y, Krepler C, Belser E, Lopez-Coral A, Xu X, Zhang G, Azuma R, Liu Q, Liu R, Li L, Amaravadi RK, Xu W, Karakousis G, Gangadhar TC, Schuchter LM, Lieu M, Khare S, Halloran MB, Herlyn, M, Kaufman, R. BRAF inhibition stimulates melanoma-associated macrophages to drive tumor growth. Clin Cancer Res. 2015;21:1652-1664. PMID25617424

Joshi S, Wels C, Beham-Schmid C, Fukunaga-Kalabis M, Holmen SL, Otte M, Herlyn M, Waldhoer M, Schaider H. Gα13 mediates human cytomegalovirus-encoded chemokine receptor US28-induced cell death in melanoma. Int J Cancer. [Epub ahead of print, 6 Mar. 2015] PMID25754407

Fukunaga-Kalabis M, Hristova DM, Wang JX, Li L, Heppt MV, Wei Z, Gyurdiev A, Webster MR, Oka M, Weeraratna AT, Herlyn M. UV-induced Wnt7a in the human skin microenvironment specifies the fate of neural crest-like cells via suppression of Notch. J Invest Dermatol. 2015;135:1521-1532. PMID25705850

Liang C; FANTOM Consortium [….Herlyn M….], Forrest AR, Wagner GP. The statistical geometry of transcriptome divergence in cell-type evolution and cancer. Nat Comm. 2015;6:6066. PMID25585899

Yoshihara M, Ohmiya H, Hara S, Kawasaki S, FANTM consiortium […Herlyn M….], Hayashuzaki, Y, Itoh M, Kawaji H, Tsujikawa M, Nishida K. Discovery of molecular markers to discriminate corneal endothelial cells in the human body. PLoS One. 2015;10(3):e0117581. PMID25807145

Liu S, Tetzlaff MT, Wang T, Yang R, Xie L, Zhang G, Krepler C, Xiao M, Bequiri M, Xu W, Karakousis G, Schuchter L, Amaravadi RK, Xu W, Wei Z, Herlyn M, Yao, Y, Zhang L, Wang Y, Zhang K. Xu X. miR-200c/Bmi1 axis and epithelial-mesenchymal transition contribute to acquire resistance to BRAF inhibitor treatment. Pigment Cell Melanoma Res. 2015;28:431-41. PMID25903073

Kim H, Frederick DT, Levesque MP, Cooper ZA, Fang Y, Krepler C, Brill L, Samuels Y, Hayward NK, Perlina A, Piris A, Zhang T, Halaban R, Herlyn M, Brown KM, Wargo JA, Dummer R, Flaherty KT, Ronai ZA. Downregulation of the ubiquitin ligase RNF125 underlies resistance of melanoma cells to BRAF inhibitors via JAK1 deregulation. Cell Rep. 2015;11:1458-73. PMID26027934

Vultur A, Smalley K, Herlyn M. Melanoma. In: Gelman EP, Sawyer CL, Rauscher III FJ, eds. Molecular Oncology: Causes of Cancer and Targets for Treatment. West Nyack, NY: Cambridge University Press; 2014:698-703.

Wang T, Ge Y, Xiao M, Lopez-Coral A, Li L, Roesch A, Huang C, Alexander P, Vogt T, Xu X, Hwang W-T, Lieu M, Belser E, Liu R, Somasundaram R, Herlyn M, Kaufman RE. SECTM1 produced by tumor cells attracts human monocytes via CD7-mediated activation of the PI3K pathway. J Invest Dermatol. 2014;134:1108-1118. PMID24157461

Nallet-Staub F, Marsaud V, Li L, Gilbert C, Dodier S, Bataille V, Sudol M, Herlyn M, Mauviel A. Pro-invasive activity of the hippo pathway effectors YAP and TAZ in cutaneous melanoma. J Invest Dermatol. 2014;134:123-132. PMID23897276

Vultur A, Villanueva J, Krepler C, Rajan G, Chen Q, Li L, Gimotty P, Wilson M, Hayden J, Keeney F, Nathanson KL, Herlyn M. MEK inhibition affects STAT3 signaling and invasion in human melanoma cell lines. Oncogene. 2014;33:1850-1861. PMID23624919 (PMC3769503)

Geserick P, Herlyn M, Leverkus M. On the TRAIL to overcome BRAF-inhibitor resistance. J Invest Dermatol. 2014;134:315-8. PMID24424456

Ma X-H, Pioa S-F, Dey S, Mcafee Q, Karakousis G, Villanueva J, Hart LS, Levi S, Hu J, Zhang G, Lazova R, Klump V, Pawelek JM, Xu X, Schuchter LM, Davies MA, Herlyn M, Winkler J, Koumenis C, Amaravadi RK. Targeting ER stress induced autophagy overcomes resistance to BRAF inhibition in melanoma. J Clin Invest. 2014;124:1406-1417. PMID24569374

Peng H, Talebzadeh-Farrooji M, Osborne MJ, Prokop JW, McDonald PC, Karar J, Hou Z, He M, Kebebew E, Orntoft T, Herlyn M, Caton AJ, Fredericks W, Malkowicz B, Paterno CS, Carolin AS, Speicher DW, Skordalakes E, Huang Q, Dedhar S, Borden KL, Rauscher FJ 3rd. LIMD2 is a small LIM-only protein overexpressed in metastatic lesions that regulates cell motility and tumor progression by directly binding to and activating the integrin-linked kinase. Cancer Res. 2014;74:1390-1403. PMID24590809

Arner E, Forrest AR, Ehrlund A, Mejhert N, Itoh M, Kawaji H, Lassmann T, Laurencikiene J, Rydén M, Arner P, FANTOM Consortium (…Herlyn M…). Ceruloplasmin is a novel adipokine which is overexpressed in adipose tissue of obese subjects and in obesity-associated cancer cells. PLoS One. 2014;9(3):e80274. PMID24676332

Hasegawa Y, Tang D, Takahashi N, Hayashizah Y, Forrest AR, FANTOM Consortium (…Herlyn M…), Suzuki H. CCL2 enhances pluripotency of human induced pluripotent stem cells by activating hypoxia related genes. Sci Rep. 2014;4:5228. PMID24957798

Yang R, Zhend Y, Li L, Liu S, Spata M, Wei Z, Nace A, Herlyn M, Cui R, Guo W, Cotsarelis G, Xu X. Direct conversion of mouse and human fibroblasts to functional melanocytes by defined factors. Nat Comm. 2014;5:5807. PMID25510211

Ravindran Menon D, Das S, Krepler C, Vultur A, Rinner B, Schauer S, Kashofer K, Wagner K, Zhang G, Rad BE, Hass N, Soyer P, Gabrielli B, Somasundaram R, Hoefler G, Herlyn M, Schaider H. A stress-induced early innate response causes multi-drug tolerance in melanoma. Oncogene. 2014;1-12. PMID25619837

Slipicevic A, Somasundaram S, Sproesser K, Herlyn M. Isolation of melanoma subpopulations using negative selection. Methods Mol Biol. 2014;1102:501-512. PMID24258995

Liu J, Fukunaga-Kalabis M, Li L, Herlyn M. Developmental pathways activated in melanocytes and melanoma. Arch Biochem Biophys. 2014;563C:13-21. PMID25109840

Zhang G, Herlyn M. Linking SOX10 to slow-growth resistance phenotype. Cell Res. 2014;24:906-907. PMID24853952

Somasundaram R, Herlyn M. Indomethacin to the rescue of TRAIL-resistant melanomas. J Invest Dermatol. 2014;134:1198-1199. PMID24732334

Andersson R, Gebhard C,Miguel-Escalada I, Hoof I, Bornholdt J, Boyd M, Chen Y, Zhao X, Schmidl C, Suzuki T, Ntini E, Arner E, Valen E, Li K, Schwarzfischer L, Glatz D, Raithel J, Lilje B, Rapin N, Bagger FO, Jørgensen M, Andersen PR, Bertin N, Rackham O, Burroughs AM, Baillie JK, Ishizu Y, Shimizu Y, Furuhata E, Maeda S, Negishi Y, Mungall CJ, Meehan TF, Lassmann T, Itoh M, Kawaji H, Kondo N, Kawai J, Lennartsson A, Daub CO, Heutink P, Hume DA, Jensen TH, Suzuki H, Hayashizaki Y, Müller F; FANTOM Consortium (…Herlyn M…), Forrest AR, Carninci P, Rehli M, Sandelin A. An atlas of active enhancers across human cell types and tissues. Nature. 2014;27;507(7493):455-61. PMID24670763

Morikawa H, Ohkura N, Vandenbon A, Itoh M, Nagao-Sato S, Kawaji H, Lassmann T, Carninci P, Hayashizaki Y, Forrest AR, Standley, DM, Date H, Sakaguchi S; FANTOM Consortium (…Herlyn M…). Differential roles of epigenetic changes and Foxp3 expression in regulatory T cell-specific transcriptional regulation. Proc Natl Acad Sci USA. 2014;111:5289-5294. PMID24706905

Hayashizaki Y, Forrest A, Kawaji H, Rehli M, Baillie J, de Hoonn M, Haberle V, Lassmann T, Kulakovskiy I, Lizio M, Itoh M, Andersson R, Mungall C, Meehan T, Freeman T, Schmeier S, Bertin N, Jørgensen M, Dimont E, Arner E, Schaefer U, Medvedeva Y, Taylor M, Francescatto M, Vitezic M, Severin J, Semple C, Ishizu Hayashizaki Y, Forrest A, Kawaji H, Rehli M, Baillie J, de Hoonn M, haberle V, Lassmann T, Kulakovskiy I, Lizio M, Itoh M, Andersson R, Mungall C, Meehan T, Freeman T, Schmeier S, Bertin N, Jørgensen M, Dimont E, Arner E, Schaefer U, Medvedeva Y, Taylor M, Francescatto M, Vitezic M, Severin J, Semple C, Ishizu Y, Kaiho A, Saka A, Hasegawa A, Knox A, Mackay-Sim A, Edge A, Bonetti A, Diehl A, Favorov A, Meynert A, Saxena A, Joshi A, Califano A, Lennartsson A, Gibson A, Kwon A, Schwegmann A, Beckhouse A, Mathelier A, Blumenthal A, Sajantila A, Pain A, Kasianov A, Kubosaki A, Manabe R, Bodega B, Marchand B, Jankovich B, Cannistraci CV, Davis C, Furlanello C, Plessy C, Kai C, Schmidl C, Wells C, Mummery C, Schneider C, Sugiyama D, Goldowitz D, de Lima Morais D, Albanese D, Vijayan D, Ovchinnikov D, Valen E, Dalla E, Wood E, Saijyo E, Schultes E, van Nimwegen E, Wolvetangg E, Drabløs D, Brombacher F, Hori F, Nakahara F, Altschuler G, Faulkner G, Jurman G, Schulze-Tanzil G, Sheng G, Fang H, Clevers H, Koseki H, Persson H, Enomoto H, Tatsukawa H, Sato H, Ohmiya H, Morikawa H, Nishiyori H, Satoh H, Toyoda H, Kawamoto H, Ohno H, Tanaka H, Carbajo D, Shimoji H, Motohashi H, Jia H, Hoof I, Vorontsov I, Alam I, Briggs J, Prendergast J, Shin J, Harshbarger J, Laros J, Mar J, Archer J, Ramilowski J, Blake J, Kempfle J, Kere J, Gough J, Takai J, Furusawa J, Li K, Kaida K, Ekwall K, Kajiyama K, Moro K, Iida K, Hitchens K, Nakazato K, Summers K, Lipovich L, Khachigian L, Winteringham L, Huminiecki L, Babina M, Fisher M, Rashid M, van de Wetering M, Chierici M, Roncador M, Patrikakis M, Okada-Hatakeyama M, Thompson M, Frith M, Farach-Carson M, Furuno M, Hamaguchi M, Suzuki M, Yamamoto M, Harbers M, Edinger M, Burroughs AM, Herlyn M, Detmar M, Fagiolini M, Tagami M, Kojima M, Yoneda M, Endoh M, Ohshima M, Hara M, Morimoto M, Murata M, Sakai M, Rye M, Kanamori-Katayama M, Ohkura N, Takahashi N, Kondo N, Mejhert N, Ninomiya N, Hofmann O, Rackham O, Rizzu P, ‘t Hoen P, Arner P, Zhang P, Klinken P, Balwierz P, Guler R, Fujita R, Passier R, Verardo R, Swoboda R, Kato S, Baker S, Krampitz S, Nagao-Sato S, Ho Sui S, Yoshida S, Koyasu S, Sakaguchi S, Katayama S, Fukuda S, Noma S, Watanabe S, Kawaguchi S, Piazza S, Zucchelli S, Kojima S, Ogishima S, Gustincich S, Roy S, Zabierowski S, Savvi S, Guhl S, Pradhan Bhatt S, Nozaki T, Dohi T, Sugiyama T, Hashimoto T, Toyoda T, Geijtenbeek T, Sengstag T, Gingeras T, Ha T, Ravasi T, Ikawa T, Kenna T, Kitamura T, Nakamura T, Kawashima T, Orlando V, Lee W, Wasserman W, Zhao W, Ciani Y, Okazaki Y, Shimoni Y, Yonekura Y, Yamaguchi Y, Mizuno Y, Hasegawa Y, Kawamura Y, Nakamura Y, Chen Y, Nakachi Y, Tatum Z, Suzuki H, Daub C, Kawai J, Heutink P, Hide W, Lenhard B, Bajic V, Makeev V, Sandelin A, Hume D, Carninci P, van den Berg L, Fairbairn L, Kaczkowski B, Lilje B, Simon C, Motakis E, Kasukawa T, Arakawa T, Suzuki N, Young R. A promoter level mammalian expression atlas. Nature. 2014;507:462-470. PMID24670764

Somasundaram R, Herlyn M. Relapse of melanoma after successful adoptive T-cell therapy: escape through inflammation-induced phenotypic melanoma plasticity. Pigment Cell Melanoma Res. 2013;26:2-4.

Balaburski GM, Leu JI, Beeharry N, Hayik S, Andrake MD, Zhang G, Herlyn M, Villanueva J, Dunbrack RL, Yen T, George DL, Murphy ME. A modified HSP70 inhibitor shows broad activity as an anticancer agent. Mol Cancer Res. 2013;11:219-229.

Krepler C, Chunduru SK, Halloran MB, He X, Xiao M, Vultur A, Villanueva J, Mitsuuchi Y, Neiman EM, Benetatos C, Nathanson KL, Amaravadi RK, Pehamberger H, McKinlay M, Herlyn M. The novel SMAC inhibitor birinapant exhibits potent activity against human melanoma cells. Clin Cancer Res. 2103;19:1784-1794.

Wang T, Somasundaram R, Herlyn M. Combination therapy of immunocytokines with Ipilimumab: a cure for melanoma? J Invest Dermatol. 2013;133(3):595-596.

Li L, Fukunaga-Kalabis M, Herlyn M. Isolation, characterization, and differentiation of human multipotent dermal stem cells. Methods Mol Biol. 2013;989:235-246.

Swoboda R, Herlyn M. There is a world beyond protein mutations: the role of non-coding RNAs in melanomagenesis. Exp Dermatol. 2013;22:303-306.

Wang T, Herlyn M. The macrophage: a new factor in UVR-induced melanomagenesis. J Invest Dermatol. 2013;133:1711-1713.

Vultur A, Herlyn M. Snapshot: melanoma. Cancer Cell. 2013;23:706.

Merlino G, Flaherty K, Acquavella N, Day CP, Aplin A, Homen S, Topalian S, Van Dyke T, Herlyn M. The future of preclinical mouse models in melanoma treatment is now. Pigment Cell Melanoma Res. 2013;26:E8-E14.

Kastl A, Dieckman S, Wähler K, Völker T, Kastl L, Shannan B, Harms K, Ocker M, Parak W, Herlyn M, Meggers E. Rhenium complexes with visible-light-induced anticancer activity. Organometallic Med Chem. 2013;8:924-927.

Desai BM, Villanueva J, Nguyen T-TK, Lioni M, Xiao M, Kong J, Krepler C, Vultur A, Flaherty KT, Nathanson KL, Smalley KSM, Herlyn M. The anti-melanoma activity of dinaciclib, a cyclin-dependent kinase inhibitor, is dependent on p53 signaling. PLoS One. 2013;8(3):e59588.

Vultur A, Villanueva J, Krepler C, Rajan G, Chen Q, Li L, Gimotty P, Wilson M, Hayden J, Keeney F, Nathanson KL, Herlyn M. MEK inhibition affects STAT3 signaling and invasion in human melanoma cell lines. Oncogene. 2013;33:1850-61. PMID23624919 (PMCID3769503)

Aird KM, Zhang G, Li H, Tu Z, Bitler BG, Garipov A, Wu H, Wei Z, Wagner SN, Herlyn M, Zhang R. Suppression of nucleotide metabolism underlies the establishment and maintenance of oncogene-induced senescence. Cell Rep. 2013;3:1-4.

Roesch A, Vultur A, Bogeski I, Wang H, Zimmermann KM, Speicher D, Körbel C, Laschke MW, Gimotty PA, Philipp SE, Krause E, Pätold S, Villanueva J, Krepler C, Fukunaga-Kalabis M, Hoth M, Bastian B, Vogt T, Herlyn M. Overcoming intrinsic multi-drug resistance in melanoma by blocking the mitochondrial respiratory chain of slow-cycling JARID1B(high) cells. Cancer Cell. 2013;23:811-825.

Reuveni H, Flashner-Abramson E, Steiner L, Makedonski K, Song R, Shir A, Herlyn M, Bar-Eli M, Levitzki A. Therapeutic destruction of insulin receptor substrates for cancer treatment. Cancer Res. 2013;73:4383-4394.

Kwak J, Gallagher M, Ozdener MH, Wysocki CJ, Goldsmith BR, Isamah A, Faranda A, Fakharzadeh SS, Herlyn M, Johnson ATC, Preti G. Volatile biomarkers from human melanoma cells. J Chromatography B Analyt Technol Biomed Life Sci. 2013;931:90-96.

Villanueva J, Infante J, Krepler C, Reyes-Uribe P, Samanta M, Chen H-Y, Li B, Swoboda R, Wilson M, Vultur A, Fukunaga-Kalabis M, Wubbenhorst B, Chen TY, Liu Q, Sproesser K, DeMarini D, Gilmer T, Martin A-M, Marmorstein R, Schultz D, Speicher D, Karakousis G, Xu W, Amaravadi R, Xu X, Schuchter L, Herlyn M, Nathanson K. Concurrent MEK2 mutation and BRAF amplification confer resistance to BRAF and MEK inhibitors in melanoma. Cell Reports. 2013;4:1090-1099.

Basu D, Bewley AF, Sperry SM, Montone KT, Gimotty PA, Rasanen K, Facompre ND, Weinstein GS, Nakagawa H, Diehl JA, Rustgi AK, Herlyn M. EGFR inhibition promotes an aggressive invasion pattern mediated by mesenchymal-like tumor cells within squamous cell carcinomas. Molec Cancer Ther. 2013;12:2176-2186.

Lee EK, Lian Z, D’Andrea K, Letrero R, Sheng W, Liu S, Diehl N, Barbash O, Schuchter LM, Amaravadi RK, Xu X, Herlyn M, Nathanson KL, Diehl JA. The FBXO4 tumor suppressor functions as a barrier to BRAFV600E-dependent metastatic melanoma. Mol Cell Biol. 2013;33:4422-4433.

Rasänen K, Speicher K, Valiga A, Tang H-Y, Zhang G, Perego M, Somasundaram R, Li L, Sriwasdi S, Klein-Szanto A, Basu D, Rustgi AK, Speicher DW, Herlyn M. Comparative secretome analysis of epithelial and mesenchymal subpopulations of head and neck squamous cell carcinoma identifies S100A4 as a potential therapeutic target. Molec Cell Proteomics. 2013;12(12):3778-92.

Wang T, Ge Y, Xiao M, Lopez-Coral A, Li L, Roesch A, Huang C, Alexander P, Vogt T, Xu X, Hwang W-T, Lieu M, Belser E, Liu R, Somasundaram R, Herlyn M, Kaufman RE. SECTM1 produced by tumor cells attracts human monocytes via CD7-mediated activation of the PI3K pathway. J Invest Dermatol. 2013 Oct 24 [Epub ahead of print].

Wong GS, Lee JS, Park YY, Klein-Szanto AJ, Waldron TJ, Cukierman E, Herlyn M,
Gimotty P, Nakagawa H, Rustgi AK. Periostin cooperates with mutant p53 to mediate invasion through the induction of STAT1 signaling in the esophagus tumor microenvironment. Oncogenesis. 2013;2:e59.

O’Connell M, Marchbank K, Webster M, Valiga A, Kaur A, Vultur A, Li L, Herlyn M, Villanueva J, Liu Q, Yin X, Widura S, Nelson J, Ruiz N, Camilli T, Indig FE, Flaherty K, Wargo J, Frederick DT, Cooper Z, Nair S, Amaravadi R, Schuchter L, Karakousis G, Xu W, Xu X, Weeraratna AT. Hypoxia induces phenotypic plasticity and therapy resistance in melanoma via the tyrosine kinase receptors ROR1 and ROR2. Cancer Disc. 2013;3(12):1378-93.

University of Utah

Division of Genetic Epidemiology

University of Utah School of Medicine
391 Chipeta Way, Suite D
Salt Lake City, UT 84103

Group Leader

Professor Lisa Cannon Albright, PhD
E-mail:
lisa@genepi.med.utah.edu
Phone: 01 801 587-9300
Fax: 01 801 581-6052

Group Members

Professor Craig Teerlink, PhD – Analysis Group Leader
Jeff Stevens – bioinformaticist
Jim Farnham – biostatistician
Steven Backus – Database Manager
Kim Nguyen – Lab Manager

Research

The Cannon-Albright lab is active in many disease areas, with a major focus on cancer. Using unique and large genealogical databases we explore the genetics of health-related phenotypes.  We study of high-risk pedigrees to identify disease predisposition genes or variants.

We ascertain and recruit high-risk pedigrees identified in the Utah Population Database, or UPDB, which combines computerized genealogies of Utah with statewide medical data (e.g. Utah Cancer Registry from 1966, Utah Death Certificates from 1904, UUHSC diagnosis and procedure coding from 1994). Along with looking for predisposition genes for melanoma, we are active in gene identification efforts for prostate cancer, colon cancer, Ewing sarcoma, pancreas cancer, bladder cancer, diabetes, stroke, alzheimers, longevity, and lung cancer.  We have stored over 35,000 DNAs from informative members of thousands of high-risk pedigrees for many phenotypes. The entire lab is funded almost exclusively by external funding agencies including NIH, DOD, and VHA.

Publications

Cannon-Albright LA, Goldgar DE, Wright EC, Turco A, Jost M, Meyer LJ, Piepkorn M, Zone JJ, Skolnick MH. (1990). Evidence against the reported linkage of the cutaneous melanoma-dysplastic nevus syndrome locus to chromosome Ip36. Am J Hum Genet46(5), 912-8.

Ahmed I, Piepkorn M, Goldgar DE, Cannon-Albright LA, Meyer LJ, Skolnick MH, Zone JJ. (1991). HMB-45 staining of dysplastic melanocytic nevi in melanoma risk groups. J Cutan Pathol18(4), 257-60.

Goldgar DE, Cannon-Albright LA, Meyer LJ, Piepkorn MW, Zone JJ, Skolnick MH. (1991). Inheritance of nevus number and size in melanoma and dysplastic nevus syndrome kindreds. J Natl Cancer Inst83(23), 1726-33.

Goldgar DE, Cannon-Albright LA, Meyer LJ, Piepkorn MW, Zone JJ, Skolnick MH. (1992). Inheritance of nevus number and size in melanoma/DNS kindreds. Cytogenet Cell Genet59(2-3), 200-2.

Cannon-Albright LA, Goldgar DE, Meyer LJ, Lewis CM, Anderson DE, Fountain JW, Hegi ME, Wiseman RW, Petty EM, Bale AE, et al. (1992). Assignment of a locus for familial melanoma, MLM, to chromosome 9p13-p22. Science258(5085), 1148-52.

Kamb A, Shattuck-Eidens D, Eeles R, Liu Q, Gris NA, Ding W, Hussey C, Tran T, Miki Y, Weaver-Feldhaus J, McClure M, Aitken JF, Anderson DE, Bergman W, Frants R, Goldgar DE, Green A. MacLennan R, Martin NG, Meyer LJ, Youl P, Zone JJ, Skolnick MH, Cannon-Albright LA. (1994). Analysis of the p16 gene (CDKN2) as a candidate for the chromosome 9p melanoma susceptibility locus. Nat Genet8(1), 23-6.

Skolnick MH, Cannon-Albright LA, Kamb A. (1994). Genetic predisposition to melanoma. Eur J Cancer30A(13), 1991-5.

Cannon-Albright LA, Goldgar DE, Neuhausen S, Gruis NA, Anderson DE, Lewis CM, Jost M, Tran TD, Nguyen K, Kamb A, Weaver-Feldhaus J, Meyer LJ, Zone JJ, Skolnick MH. (1994). Localization of the 9p melanoma susceptibility locus (MLM) to a 2-cM region between D9S736 and D9S171. Genomics23(1), 265-8.

Cannon-Albright LA, Meyer LJ, Goldgar DE, Lewis CM, McWhorter WP, Jost M, Harrison D, Anderson DE, Zone JJ, Skolnick MH. (1994). Penetrance and expressivity of the chromosome 9p melanoma susceptibility locus (MLM). Cancer Res54(23), 6041-4.

Cannon-Albright LA, Kamb A, Skolnick M. (1996). A review of inherited predisposition to melanoma. Semin Oncol23(6), 667-72.

Florell SR, Meyer LJ, Boucher KM, Porter-Gill PA, Hart M, Erickson J, Cannon-Albright LA, Pershing LK, Harris RM, Samlowski WE, Zone JJ, Leachman SA. (2004). Longitudinal assessment of the nevus phenotype in a melanoma kindred. J Invest Dermatol123(3), 576-82.

Florell SR, Meyer LJ, Boucher KM, Hart M, Cannon-Albright LA, Harris RM, Grossman D, Samlowski WE, Zone JJ, Brinton JP, Leachman SA. (2005). Nevus distribution in a Utah melanoma kindred with a temperature-sensitive CDKN2A mutation. J Invest Dermatol125(6), 1310-2.

Florell SR, Boucher KM, Garibotti G, Astle J, Kerber R, Mineau G, Wiggins C, Noyes RD, Tsodikov A, Cannon-Albright LA, Zone JJ, Samlowski WE, Leachman SA. (2005). Population-based analysis of prognostic factors and survival in familial melanoma. J Clin Oncol23(28), 7168-77.

Eliason MJ, Larson AA, Florell SR, Zone JJ, Cannon-Albright LA, Samlowski WE, Leachman SA. (2006). Population-based prevalence of CDKN2A mutations in Utah melanoma families. J Invest Dermatol126(3), 660-6.

Goldstein AM, Chan M, Harland M, Gillanders EM, Hayward NK, Avril MF, Azizi E, Bianchi-Scarra G, Bishop DT, Bressac-de Paillerets B, Bruno W, Calista D, Cannon Albright LA, Demenais F, Elder DE, Ghiorzo P, Gruis NA, Hansson J, Hogg D, Holland EA, Kanetsky PA, Kefford RF, Landi MT, Lang J, Leachman SA, Mackie RM, Magnusson V, Mann GJ, Niendorf K, Newton Bishop J, Palmer JM, Puig S, Puig-Butille JA, de Snoo FA, Stark M, Tsao H, Tucker MA, Whitaker L, Yakobson E, Melanoma Genetics Consortium (GenoMEL). (2006). High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL. Cancer Res66(20), 9818-28.

Goldstein AM, Chan M, Harland M, Hayward NK, Demenais F, Bishop DT, Azizi E, Bergman W, Bianchi-Scarra G, Bruno W, Calista D, Albright LA, Chaudru V, Chompret A, Cuellar F, Elder DE, Ghiorzo P, Gillanders EM, Gruis NA, Hansson J, Hogg D, Holland EA, Kanetsky PA, Kefford RF, Landi MT, Lang J, Leachman SA, MacKie RM, Magnusson V, Mann GJ, Bishop JN, Palmer JM, Puig S, Puig-Butille JA, Stark M, Tsao H, Tucker MA, Whitaker L, Yakobson E, Lund Melanoma Study Group, Melanoma Genetics Consortium (GenoMEL). (2007). Features associated with germline CDKN2A mutations: a GenoMEL study of melanoma-prone families from three continents. J Med Genet44(2), 99-106.

Larson AA, Leachman SA, Eliason MJ, Cannon-Albright LA. (2007). Population-Based Assessment of Non-Melanoma Cancer Risk in Relatives of Cutaneous Melanoma Probands. J Invest Dermatol127(1), 183-8.

Eliason MJ, Hansen CB, Hart M, Porter-Gill P, Chen W, Sturm RA, Bowen G, Florell SR, Harris RM, Cannon-Albright LA, Swinyer L, Leachman SA. (2007). Multiple primary melanomas in a CDKN2A mutation carrier exposed to ionizing radiation. Arch Dermatol143(11), 1409-12.

Florell SR, Meyer LJ, Boucher KM, Grossman D, Cannon-Albright LA, Harris RM, Samlowski WE, Zone JJ, Leachman SA. (2008). Increased Melanocytic Nevi and Nevus Density in a G-34T CDKN2A/p16 Melanoma-Prone Pedigree. J Invest Dermatol128(8), 2122-2125.

Bishop DT, Demenais F, Iles MM, Harland M, Taylor JC, Corda E, Randerson-Moor J, Aitken JF, Avril MF, Azizi E, Bakker B, Bianchi-Scarrà G, Bressac-de Paillerets B, Calista D, Cannon-Albright LA, Chin-A-Woeng T, Debniak T, Galore-Haskel G, Ghiorzo P, Gut I, Hansson J, Hocevar M, Höiom V, Hopper JL, Ingvar C, Kanetsky PA, Kefford RF, Landi MT, Lang J, Lubiński J, Mackie R, Malvehy J, Mann GJ, Martin NG, Montgomery GW, van Nieuwpoort FA, Novakovic S, Olsson H, Puig S, Weiss M, van Workum W, Zelenika D, Brown KM, Goldstein AM, Gillanders EM, Boland A, Galan P, Elder DE, Gruis NA, Hayward NK, Lathrop GM, Barrett JH, Bishop JA. (2009). Genome-wide association study identifies three loci associated with melanoma risk. Nat Genet41(8), 920-5

Barrett JH, Iles MM, Harland M, Taylor JC, Aitken JF, Andresen PA, Akslen LA, Armstrong BK, Avril MF, Azizi E, Bakker B, Bergman W, Bianchi-Scarra G, Bressac-de Paillerets B, Calista D, Cannon-Albright LA, Corda E, Cust AE, Debniak T, Duffy D, Dunning AM, Easton DF, Friedman E, Galan P, Ghiorzo P, Giles GG, Hansson J, Hocevar M, Hoiom V, Hopper JL, Ingvar C, Janssen B, Jenkins MA, Jonsson G, Kefford RF, Landi G, Landi MT, Lang J, Lubinski J, Mackie R, Malvehy J, Martin NG, Molven A, Montgomery GW, van Nieuwpoort FA, Novakovic S, Olsson H, Pastorino L, Puig S, Puig-Butille JA, Randerson-Moor J, Snowden H, Tuominen R, Van Belle P, van der Stoep N, Whiteman DC, Zelenika D, Han J, Fang S, Lee JE, Wei Q, Lathrop GM, Gillanders EM, Brown KM, Goldstein AM, Kanetsky PA, Mann GJ, Macgregor S, Elder DE, Amos CI, Hayward NK, Gruis NA, Demenais F, Bishop JA, Bishop DT. (2011). Genome-wide association study identifies three new melanoma susceptibility loci. Nat Genet43(11), 1108-13.

Teerlink C, Farnham J, Allen-Brady K, Camp NJ, Thomas A, Leachman S, Cannon-Albright L. (2012). A unique genome-wide association analysis in extended Utah high-risk pedigrees identifies a novel melanoma risk variant on chromosome arm 10q. Hum Genet131(1), 77-85.

Hawkes JE, Campbell J, Garvin D, Cannon-Albright L, Cassidy P, Leachman SA. (2013). Lack of GNAQ and GNA11 Germ-Line Mutations in Familial Melanoma Pedigrees with Uveal Melanoma or Blue Nevi. Front Oncol3:160.

Hawkes JE, Cassidy PB, Manga P, Boissy RE, Goldgar D, Cannon-Albright L, Florell SR, Leachman SA. (2013). Report of a novel OCA2 gene mutation and an investigation of OCA2 variants on melanoma risk in a familial melanoma pedigree. J Dermatol Sci69(1), 30-7.

Taylor NJ, Handorf EA, Mitra N, Avril MF, Azizi E, Bergman W, Bianchi-Scarrà G, Bishop DT, Bressac-de Paillerets B, Calista D, Cannon-Albright LA, Cuellar F, Cust AE, Demenais F, Elder DE, Friedman E, Gerdes AM, Ghiorzo P, Goldstein AM, Grazziotin TC, Hansson J, Hayward NK, Hocevar M, Höiom V, Holland EA, Ingvar C, Landi MT, Landman G, Larre-Borges A, Leachman SA, Mann GJ, Nagore E, Olsson H, Palmer J, Perić B, Pjanova D, Puig S, Schmid H, van der Stoep N, Tucker MA, Wadt KA, Whitaker L, Yang XR, Newton Bishop JA, Gruis NA, Kanetsky PA; GenoMEL Consortium.  Phenotypic and histopathological tumor characteristics according ot CDKN2A mutation status among affected members of melanoma families.  J Invest Dermatol. 2016 Jan 28.

National Cancer Institute, Maryland

Our institution

National Cancer Institute


Our group

American Melanoma Families Group
Genetic Epidemiology Branch
Division of Cancer Epidemiology and Genetics
National Cancer Institute
NIH/DHHS
Executive Plaza South
6120 Executive Blvd.
Bethesda, MD 20892-7236
USA


The Group leader

Alisa M. Goldstein, Ph.D.
Genetic Epidemiology Branch
Division of Cancer Epidemiology and Genetics
National Cancer Institute
NIH/DHHS
Executive Plaza South
6120 Executive Blvd.
Bethesda, MD 20892-7236
USA

Tele: 01-301-496-4375
Fax: 01-301-402-4489
Email: goldstea@mail.nih.gov


Our studies of familial melanoma began in the mid 1970’s as a clinical and epidemiologic evaluation of American families with two or more living members with melanoma. The study has evolved over the years to a more formal genetic epidemiologic investigation of families with three or more living members with melanoma. We have examined and followed over 2000 family members, some for over 25 years. We are actively accruing additional families in the U.S. and can be contacted at the above address.

Participants are evaluated either at the NIH Clinical Center or locally by the study team. The research team currently includes genetic epidemiologists, clinicians (physicians and nurses), and laboratory investigators. The major goals of the study are to investigate the genetic and environmental determinants of melanoma in families without known germline mutations; for families with CDKN2A mutations, to study the contribution of other genetic and environmental factors in the expression of disease, to estimate penetrance, and to examine gene-gene and gene-environment interactions.


The names and e-mail addresses of the group members

Principal researchers

Margaret Tucker, MD
tuckerp@mail.nih.gov

Alisa Goldstein, PhD
goldstea@mail.nih.gov

Maria Teresa Landi, MD, PhD
landim@mail.nih.gov

Elizabeth Gillanders, PhD
Elizabeth.Gillanders@nih.gov

Rose Yang
royang@mail.nih.gov

Research Nurse

Mary Fraser
fraserm@mail.nih.gov


Publications

Newton Bishop JA, Harland M, Bennett DC, Bataille V, Goldstein AM, Tucker MA, Ponder BAJ, Cuzick J, Selby P, Bishop DT.
Mutation testing in melanoma families: INK4A, CDK4, and INK4D.
Br J Cancer 1999;80:295-300.

Shennan MG, Badin AC, Walsh S, Summers A, From L, McKenzie M, Goldstein AM, Tucker MA, Hogg D, Lassam N.
Lack of germline CDK6 mutations in familial melanoma.
Oncogene 2000;19:1849-1852.

Goldstein AM, Struewing JP, Chidambaram A, Fraser MC, Tucker MA.
Genotype-phenotype relationships in U.S. melanoma-prone families with CDKN2A and CDK4 mutations.
J Natl Cancer Inst 2000;92:1006-1010.

Harland M, Holland EA, Ghiorzo P, Mantelli M, Bianchi-Scarra G, Goldstein AM, Tucker MA, Ponder BAJ, Mann GJ, Bishop DT, Newton Bishop J.
Mutation screening of the CDKN2A promoter in melanoma families.
Genes Chromosomes Cancer 2000;28:45-57.

Ciotti P, Struewing JP, Mantelli M, Chompret A, Avril MF, Santi PL, Tucker MA, Bianchi-Scarra G*, Bressac-de Paillerets B*, Goldstein AM*.
A single genetic origin for the G101W CDKN2A mutation in 20 melanoma-prone families.
Am J Hum Genet 2000;67:311-319.

Goldstein AM, Martinez M, Tucker MA, Demenais F.
Gene-covariate interaction between dysplastic nevi and the CDKN2A gene in American melanoma-prone families.
Cancer Epidemiol Biomarkers Prev 2000;9:889-894.

Auroy S, Avril MF, Chompret A, Pham D, Goldstein AM, Bianchi-Scarra G, Frebourg T, Joly P, Spatz SA, Rubino C, Demenais F, French
Hereditary Melanoma Study Group, Bressac-de Paillerets B. Sporadic multiple primary melanoma cases: CDKN2A germline mutations with a founder effect.
Genes Chromosomes Cancer 2001;32:195-202.

Goldstein AM, Liu L, Shennan MG, Hogg D, Tucker MA, Struewing JP.
A common founder for the V126D CDKN2A mutation in seven North American melanoma-prone families.
Br J Cancer 2001;85:527-530.

Goldstein AM, Tucker MA.
Genetic epidemiology of cutaneous melanoma – A global perspective.
Arch Dermatol 2001;137:1493-1496.

Mantelli M, Barile M, Ciotti P, Ghiorzo P, Lantieri F, Pastorino L, Catricalà C, Torre GD, Folco U, Grammatico P, Padovani L, Pasini B, Rovini D, Queirolo P, Rainero ML, Santi PL, Sertoli RM, Goldstein AM, Società Italiana Dermatologia e Venerologia Gruppo Italiano Studi Epidemiologici in Dermatologia, Bianchi-Scarrà G.
High prevalence of the G101W germline mutation in the CDKN2A (P16ink4a) gene in 62 Italian malignant melanoma families.
Am J Med Genet 2002;107:214-221.

Tucker MA, Fraser MC, Goldstein AM, Struewing JP, King MA, Crawford JT, Chiazze EA, Zametkin DP, Fontaine LS, Clark WH, Jr.
A natural history of melanomas and dysplastic nevi: An atlas of lesions in melanoma-prone families.
Cancer 2002;94:3192-3209.

Bishop DT*, Demenais F*, Goldstein AM*, Bergman W, Bishop JN, Bressac-de Paillerets B, Chompret A, Ghiorzo P, Gruis N, Hansson J, Harland M, Hayward N, Holland EA, Mann GJ, Mantelli M, Nancarrow D, Platz A, Tucker MA, The Melanoma Genetics Consortium.
Geographical variation in the penetrance of CDKN2A mutations for melanoma.
J Natl Cancer Inst 2002;94:894-903.

Feng Y, Shi J, Goldstein AM, Tucker MA, Nelson MA.
Analysis of mutations and identification of several polymorphisms in the putative promoter region of the p34CDC2-related CDC2L1 gene located at 1p36 in melanoma cell lines and melanoma families.
Int J Cancer 2002;99:834-838.

Kefford R, Newton Bishop J, Tucker M, Bressac-de Paillerets B, Bianchi-Scarra G, Bergman W, Goldstein A, Puig S, Mackie R, Elder D, Hansson J, Hayward N, Hogg D, Olsson H, on behalf of the Melanoma Genetics Consortium.
Genetic testing for melanoma.
Lancet Oncol 2002; 3:653-4.

Tucker MA, Goldstein AM.
Melanoma etiology: where are we?
Oncogene 2003;22:3042-3052.

Tucker MA, Fraser MC, Goldstein AM, Struewing JP, King MA, Crawford JT, Chiazze EA, Zametkin DP, Fontaine LS, Clark WH, Jr.
A natural history of melanomas and dysplastic nevi: An atlas of lesions in melanoma-prone families.
Dermatol Nursing 2003;15:237-253.

Massachusetts General Hospital

bostonpictxt

Our institution

Massachusetts General Hospital
55 Fruit Street
Boston, MA 02114; USA


Our group

Massachusetts General Hospital Melanoma Genetics ProgramTitle and address of our group

Hensin Tsao, MD PhD, Director
Department of Dermatology
Bartlett 622
48 Blossom Street
Boston, MA 02114


The Group leader

Hensin Tsao, MD PhD
Director
Department of Dermatology
Massachusetts General Hospital Melanoma Genetics Program
Bartlett 622
48 Blossom Street
Boston, MA 02114

Phone: 617-726-9569
Fax: 617-724-2745
Email: tsao.hensin@mgh.harvard.edu


The Massachusetts General Hospital Pigmented Lesion Center (MGH PLC).
The MGH PLC is the oldest continuously-operational multidisciplinary melanoma group in the United States. Established in 1966 by Dr. Thomas B. Fitzpatrick (Dermatology), Dr. John Raker (Surgery), Dr. Wallace Clark and Dr. Martin C. Mihm (Pathology), the MGH PLC was created to advance understanding of a relatively rare cancer at that time- cutaneous melanoma. The MGH PLC is co-directed by Drs. Arthur J Sober and Hensin Tsao and remains the major center for melanoma patient care for the New England area and the site of active ongoing melanoma research. The MGH PLC shares a seat with many other international melanoma centers on the World Health Organization Melanoma Programme.

As a care center, the MGH PLC evaluates over 200-300 new melanoma patients per year and attends to over 3000 visits. Additional patients are also treated and managed in the medical and surgical oncology units as well as within surgery. As a teaching site, the MGH PLC trains dermatology residents from Harvard Medical School and other rotating residents and students, postgraduate dermatopathology fellows and fully-trained physicians from around the world interested in melanocytic tumors.

The Massachusetts General Hospital Melanoma Genetics Program

In 2000, the MGH Cancer Center initiated a core group of cancer genetics programs dedicated to the research and management of patients with hereditary malignancies. The Melanoma Genetics Program emerged from this initiative and is fully integrated into the MGH PLC. The Melanoma Genetics Program provides genetic counseling services for melanoma patients and coordinates genetics research utilizing the rich patient population. The Melanoma Genetics Program is comprised of Dr. Hensin Tsao, a molecular geneticist researcher and dermatologist, Ms. Lauren Carpiniello, a genetics counselor and Dr. Arthur J. Sober, a melanoma clinical researcher and dermatologist.


Related Links

MGH Center for Cancer Risk Analysis; Melanoma Genetics Program
www.cancer.mgh.harvard.edu/cancer_riskanalysis_clinicalresearch.htm

MGH Melanoma and Pigmented Lesion Center; Melanoma Center
http://www.mgh.harvard.edu/mghdermatology/services/pigmented_lesion_center.htm


The names and e-mail addresses of group members with a description of their contribution

Director

Hensin Tsao, MD, PhD
Molecular geneticist, dermatologist
Email: tsao.hensin@mgh.harvard.edu

Lauren Marie Carpiniello
Senior Genetic Counselor
Email: lcarpiniello@partners.org

Arthur J. Sober, MD
Dermatologist
Email: asober@partners.org


Publications

Tsao H, Sober AJ.
Ultraviolet radiation and malignant melanoma.
Clin Dermatol. 1998 Jan-Feb; 16(1): 67-73. Review.

Tsao H, Benoit E, Sober AJ, Thiele C, Haluska FG.
Novel mutations in the p16/CDKN2A binding region of the cyclin-dependent kinase-4 gene.
Cancer Res. 1998 Jan 1; 58(1): 109-13.

Tsao H, Rogers GS, Sober AJ.
An estimate of the annual direct cost of treating cutaneous melanoma
J Am Acad Dermatol. 1998 May; 38(5 Pt 1): 669-80.

Tsao H, Zhang X, Benoit E, Haluska FG.
Identification of PTEN/MMAC1 alterations in uncultured melanomas and melanoma cell lines.
Oncogene. 1998 Jul 2; 16(26): 3397-402.

Tsao H, Zhang X, Majewski P, Haluska FG.
Mutational and expression analysis of the p73 gene in melanoma cell lines.
Cancer Res 1999; 59: 172-174.

Tsao H, Zhang X, Fowlkes K, Haluska FG.
Relative reciprocity of NRAS and PTEN/MMAC1 alterations in cutaneous melanoma cell lines.
Cancer Res. 2000 Apr 1; 60(7): 1800-4.

Tsao H, Zhang X, Kwitkiwski K, Finkelstein DM, Sober AJ, Haluska FG.
Low prevalence of germline CDKN2A and CDK4 mutations in patients with early onset melanoma.
Arch Dermatol. 2000 Sep; 136(9): 1118-22.

Tsao H. CME
Article: Update on familial cancer syndromes and the skin.
J Am Acad Dermatol 2000; 42: 939-969.

Tsao H, Nadiminti U, Sober AJ, Bigby M.
A meta-analysis of reverse transcriptase-polymerase chain reaction (RT-PCR) for tyrosinase mRNA as a marker for circulating tumor cells in cutaneous melanoma.
Arch Dermatol, 2001; 137:325-330.

Goggins W, Finkelstein D, Tsao H.
Evidence for an association between cutaneous melanoma and non-Hodgkin’s lymphoma.
Cancer, 2001; 91:874-80.

Niendorf KB, Shannon KM. The role of genetic testing and effect on patient care. Arch Dermatol. 2001 Nov;137(11):1515-9. 11. Sober AJ, Chuang TY, Duvic M, Farmer ER, Grichnik JM, Halpern AC, Ho V, Holloway V, Hood AF, Johnson TM, Lowery BJ;
Guidelines/Outcomes Committee. Guidelines of care for primary cutaneous melanoma.
J Am Acad Dermatol. 2001 Oct;45(4):579-86.

Tsao H.
Genetics of non-melanoma skin cancer.
Arch Dermatol; 2001; 137: 1486-1492

Tsao H, Kwitkiwski K, Sober AJ.
A single-institution case series of patients with cutaneous melanoma and non-Hodgkin’s lymphoma.
J Am Acad Dermatol; 2002; 46:55-61

Tsao H, Millman P, Linette GP, Hodi FS, Sober AJ, Goldberg MA, Haluska FG.
Hypopigmentation associated with an adenovirus-mediated gp100/MART-1-transduced dendritic cell vaccine for metastatic melanoma.
Arch Dermatol. 2002;138:799-802.

Goggins WB, Tsao H.
A population-based analysis of risk factors for a second primary cutaneous melanoma among melanoma survivors.
Cancer 2003;97:639-43

Tsao H, Bevona C, Goggins W, Quinn T.
The transformation rate of moles (melanocytic nevi) into cutaneous melanoma.
Arch Dermatol 2003;139:282-8.

Tsao H, Mihm MC, Sheehan C.
PTEN expression in normal skin, acquired melanocytic nevi and cutaneous melanoma.
J Am Acad Dermatol 2003; 49(5):865-72

Bevona C, Goggins W, Quinn T, Fullerton J, Tsao H.
Cutaneous melanomas associated with nevi.
Arch Dermatol 2003;139:1620-4

[21]. Bevona C, Sober AJ, Tsao H Chapter 15.
Childhood melanoma. In: Balch C, Houghton AN, Sober AJ, Soong SJ, eds. Cutaneous Melanoma 6th Edition.
St Louis: Quality Medical Publishing, Inc, 2003: 309-318

Tsao H, Sober AJ. Chapter 91.
Atypical Melanocytic Nevi. In: Fitzpatrick TB, et al, eds. Fitzpatrick’s Dermatology in General Medicine, 6th Edition.
New York, NY: McGraw Hill, Inc., 2003: 906-916

Tsao H, Feldman M, Fullerton JE, Sober AJ, Rosenthal D, Goggins W.
Early detection of asymptomatic pulmonary melanoma metastases by routine chest radiographs is not associated with improved survival.
Arch Dermatol 2004;140:67-70.

Tsao H, Goel V, Wu H, Yang G, Haluska FG.
Genetic interaction between NRAS and BRAF mutations and PTEN/MMAC1 inactivation in melanoma.
J Invest Dermatol. 2004 Feb; 122(2): 337-41.

Goggins W, Gao W, Tsao H.
Association between female breast cancer and cutaneous melanoma.
Int J Cancer. 2004 Sep 20; 111(5): 792-4.

Yang G, Niendorf KB, Tsao H.
A novel methionine-53-valine mutation of p16 in a hereditary melanoma kindred.
J Invest Dermatol. 2004 Sep; 123(3): 574-5.

Tsao H, Atkins MB, Sober AJ.
Management of cutaneous melanoma.
N Engl J Med. 2004 Sep 2; 351(10): 998-1012. Review. Erratum in: N Engl J Med. 2004 Dec 2; 351(23): 2461.

Tsai KY, Tsao H.
The genetics of skin cancer.
Am J Med Genet C Semin Med Genet. 2004 Nov 15; 131C(1): 82-92. Review.

Tsao H, Niendorf K.
Genetic testing in hereditary melanoma.
J Am Acad Dermatol. 2004 Nov; 51(5): 803-8. Review.

Niendorf KB, Goggins W, Yang G, Tsai KY, Shennan M, Bell DW, Sober AJ, Hogg D, Tsao H.
MELPREDICT: a logistic regression model to estimate CDKN2A carrier probability.
J Med Genet. 2006 Jun; 43(6): 501-6. Epub 2005 Sep 16.

Yang G, Rajadurai A, Tsao H.
Recurrent patterns of dual RB and p53 pathway inactivation in melanoma.
J Invest Dermatol. 2005 Dec;125(6):1242-51.

Niendorf KB, Tsao H.
Cutaneous melanoma: family screening and genetic testing.
Dermatol Ther. 2006 Jan-Feb; 19(1): 1-8. Review.

Haluska FG, Tsao H, Wu H, Haluska FS, Lazar A, Goel V.
Genetic alterations in signaling pathways in melanoma.
Clin Cancer Res. 2006 Apr 1; 12(7 Pt 2): 2301s-2307s. Review.

Yang G, Zhang G, Pittelkow MR, Ramoni M, Tsao H.
Expression profiling of UVB response in melanocytes identifies a set of p53-target genes.
J Invest Dermatol. 2006 Nov; 126(11): 2490-506. Epub 2006 Aug 3.

Goldstein AM, Chan M, Harland M, Hayward NK, Demenais F, Bishop DT, Azizi E, Bergman W, Bianchi-Scarra G, Bruno W, Calista D, Albright LA, Chaudru V, Chompret A, Cuellar F, Elder DE, Ghiorzo P, Gillanders EM, Gruis NA, Hansson J, Hogg D, Holland EA, Kanetsky PA, Kefford RF, Landi MT, Lang J, Leachman SA, MacKie RM, Magnusson V, Mann GJ, Bishop JN, Palmer JM, Puig S, Puig-Butille JA, Stark M, Tsao H, Tucker MA, Whitaker L, Yakobson E; Lund Melanoma Study Group; Melanoma Genetics Consortium (GenoMEL).
Features associated with germline CDKN2A mutations: a GenoMEL study of melanoma-prone families from three continents.
J Med Genet. 2007 Feb; 44(2): 99-106. Epub 2006 Aug 11.

Goldstein AM, Chan M, Harland M, Gillanders EM, Hayward NK, Avril MF, Azizi E, Bianchi-Scarra G, Bishop DT, Bressac-de Paillerets B, Bruno W, Calista D, Cannon Albright LA, Demenais F, Elder DE, Ghiorzo P, Gruis NA, Hansson J, Hogg D, Holland EA, Kanetsky PA, Kefford RF, Landi MT, Lang J, Leachman SA, Mackie RM, Magnusson V, Mann GJ, Niendorf K, Newton Bishop J, Palmer JM, Puig S, Puig-Butille JA, de Snoo FA, Stark M, Tsao H, Tucker MA, Whitaker L, Yakobson E; Melanoma Genetics Consortium (GenoMEL).
High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL.
Cancer Res. 2006 Oct 15; 66(20): 9818-28.

Lang J, Hayward N, Goldgar D, Tsao H, Hogg D, Palmer J, Stark M, Tobias ES, MacKie R.
The M53I mutation in CDKN2A is a founder mutation that predominates in melanoma patients with Scottish ancestry.
Genes Chromosomes Cancer. 2007 Mar; 46(3): 277-87.

Hocker T, Tsao H.
Ultraviolet radiation and melanoma: a systematic review and analysis of reported sequence variants.
Hum Mutat. 2007 Jun; 28(6): 578-88. Review.

Yang G, Curley D, Bosenberg MW, Tsao H.
Loss of xeroderma pigmentosum C (Xpc) enhances melanoma photocarcinogenesis in Ink4a-Arf-deficient mice.
Cancer Res. 2007 Jun 15; 67(12): 5649-57.

Singh M, Lin J, Hocker TL, Tsao H.
Genetics of melanoma tumorigenesis.
Br J Dermatol. 2008 Jan; 158(1): 15-21. Epub 2007 Nov 28. Review.

Zhang G, Njauw CN, Park JM, Naruse C, Asano M, Tsao H.
EphA2 is an essential mediator of UV radiation-induced apoptosis.
Cancer Res. 2008 Mar 15; 68(6): 1691-6.

Harland M, Goldstein AM, Kukalizch K, Taylor C, Hogg D, Puig S, Badenas C, Gruis N, Ter Huurne J, Bergman W, Hayward NK, Stark M, Tsao H, Tucker MA, Landi MT, Scarra GB, Ghiorzo P, Kanetsky PA, Elder D, Mann GJ, Holland EA, Bishop DT, Newton Bishop J; members of GenoMEL, the Melanoma Genetics Consortium.
A comparison of CDKN2A mutation detection within the Melanoma Genetics Consortium (GenoMEL).
Eur J Cancer. 2008 Jun; 44(9): 1269-1274. Epub 2008 Apr 3.

Lin J, Hocker TL, Singh M, Tsao H.
Genetics of melanoma predisposition.
Br J Dermatol. 2008 Jun 11.

Sun BK, Tsao H.
X-Chromosome Inactivation and Skin Disease.
J Invest Dermatol. 2008 May 29. [Epub ahead of print]