LUMC Clinical Genetics

Our institution

Leiden University Medical Center
Albinusdreef 2
2333 ZA Leiden
The Netherlands


Our group

Department of Clinical Genetics
Leiden University Medical Center
Postbus 9600
2300 RC Leiden
The Netherlands

Department of Clinical Genetics
(Laboratory)
DGA
LUMC building 2
Post zone S-06-P
PO box 9600
2300 RC Leiden


The name, address and contact e-mail, tel of the group leader

Prof. Dr. M. H. Breuning
Department of Clinical Genetics
Leiden University Medical Center
Postbus 9600
2300 RC Leiden
The Netherlands

E-mail: m.h.breuning@lumc.nl
Phone: 071-5266090 / 5266060
Fax: 071-526 6749


Our knowledge of mankind’s hereditary characteristics is growing at a tremendous pace. As a result we are becoming more and more successful at tracking down the causes of congenital defects and hereditary diseases.

The Department of Clinical Genetics at the Leiden University Medical Center (LUMC) strives to apply all of this new knowledge as quickly and well as possible in medical practice. Through close collaboration with the Department of Human Genetics at the Center for Human and Clinical Genetics (CHCG) we are able to speedily put into practice the very latest developments in the diagnosis of hereditary diseases.


Related Links

Clinical Genetics, LUMC
www.lumc.nl/4080/default_english.html

Leiden University Medical Center (LUMC)
www.lumc.nl/english/start_english.html

The Netherlands Foundation for the Detection of Hereditary Tumours
www.stoet.nl


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

Management Team Department

Mrs. Dr. C.J. van Asperen
Head Genetic Counseling Section
c.j.van_asperen@lumc.nl

Prof. Dr. E. Bakker
Head Laboratory Diagnostics sub-department
e.bakker@lumc.nl

Prof. Dr. M. H. Breuning
Head Department of Clinical Genetics
m.h.breuning@lumc.nl

Mrs. J.E.M. van Diemen-Homan
Quality Manager Genetic Counseling Section

Mrs. Drs. E. Voorhoeve
quality manager  Laboratory Diagnostics sub-department

Genetic Counselling Section

Mrs. Dr. C.J. van Asperen
head Genetic Counseling Section

Mrs. Dr. E.K. Bijlsma
clinical geneticist

Prof. Dr. M.H. Breuning
clinical geneticist

Mrs. Dr. A.H.J.T. Bröcker-Vriends
clinical geneticist

Mrs. B.T.J. van Brussel
genetic consultant

Mrs. J.E.M. van Diemen-Homan
genetic consultant

Drs. A. van Haeringen
clinical geneticist

Mrs. Drs. A.T.J.M. Helderman – v.d. Enden
clinical geneticist

Mrs. Drs. Y.M. Hendriks
medical assistant clinical genetics

Dr. F.J.H. Hes
clinical geneticist

Mrs. Drs. Y. Hilhorst-Hofstee
clinical geneticist

Mrs. Dr. N.S. den Hollander
clinical geneticist

Mrs. Dr. S.G. Kant
clinical geneticist

Mrs. Drs. M. Kriek
medical assistant clinical genetics

Mrs. Dr. S.A.M.J. Lesnik Oberstein
medical assistant clinical genetics

Mrs. A.M. van Mil
genetic consultant

Mrs. I. v.d. Schoot-van Velzen
genetic consultant in training

Mrs. Drs. F. de Snoo
medical assistant clinical genetics

Prof. Dr. A. Tibben
psychologist

 

Cytogenetics

Prof. Dr. E. Bakker
ad interim laboratory head

Mrs. Dr. K.B.M. Hansson
clinical cytogeneticist, laboratory head

Mrs. Dr. M.J.V. Hoffer
clinical cytogeneticist

Mrs. Drs. W.G.M. Kroes
clinical cytogeneticist

Mrs. Dr. C. Ruivenkamp
clinical cytogeneticist in training

Mrs. Drs. S.L. van Zelderen – Bhola
clinical cytogeneticist

Molecular Genetics

Prof. Dr. E. Bakker
laboratory head

Mrs. Dr. E.M.J. Boon
clinical molecular geneticist in training

Mrs. Dr. M.J. van Belzen
clinical molecular geneticist in training

Mrs. Dr. H.B. Ginjaar
clinical molecular geneticist

Ing. A.L.J. Kneppers
head technician

Mrs. Dr. M. Losekoot
clinical molecular geneticist, laboratory head

Mrs. Dr. C.M.J. Tops
clinical molecular geneticist

Mrs. Dr. M.M. Weiss
clinical molecular geneticist in training

Dr. J.T.H. Wijnen
clinical molecular geneticist

Hemoglobinopathies Laboratory

Dr. P.C. Giordano
clinical biochemic geneticist, laboratory head

Dr. C.L. Harteveld
clinical molecular geneticist


Publications

 Pavel S, van Nieuwpoort F, van der Meulen H, Out C, Pizinger K, Cetkovska P, Smit NP, Koerten HK.
Disturbed melanin synthesis and chronic oxidative stress in dysplastic naevi.
Eur J Cancer 2004, 40:1423-30.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15177503

Hayes MJ, Koundouris A, Gruis N, Bergman W, Peters GG, Sinclair AJ.
P16(INK4A)-independence of Epstein-Barr virus-induced cell proliferation and virus latency.
J Gen Virol. 2004, 85:1381-6.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15166419

Zuidervaart W, van der Velden PA, Hurks MH, van Nieuwpoort FA, Out-Luiting CJ, Singh AD, Frants RR, Jager MJ, Gruis NA.
Gene expression profiling identifies tumour markers potentially playing a role in uveal melanoma development.
Br J Cancer. 2003, 89:1914-9.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14612903

de Snoo FA, Bergman W, Gruis NA.
Familial melanoma: a complex disorder leading to controversy on DNA testing.
Fam Cancer. 2003,2:109-16.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14574160

de vos tot Nederveen Cappel WH, Offerhaus GJ, van Puijenbroek M, Caspers E,Gruis NA, De Snoo FA, Lamers CB, Griffioen G, Bergman W, Vasen HF, Morreau H.
Pancreatic carcinoma in carriers of a specific 19 base pair deletion of CDKN2A/p16 (p16-leiden).
Clin Cancer Res. 2003, 9:3598-605.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14506146

van der Velden PA, Zuidervaart W, Hurks MH, Pavey S, Ksander BR, Krijgsman E, Frants RR, Tensen CP, Willemze R, Jager MJ, Gruis NA.
Expression profiling reveals that methylation of TIMP3 is involved in uveal melanoma development.
Int J Cancer. 2003, 106:472-9.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12845640

 Gillanders E, Juo SH, Holland EA, Jones M, Nancarrow D, Freas-Lutz D, Sood R, Park N, Faruque M, Markey C, Kefford RF, Palmer J, Bergman W, Bishop DT,Tucker MA, Bressac-de Paillerets B, Hansson J, Stark M, Gruis N, Bishop JN,Goldstein AM, Bailey-Wilson JE, Mann GJ, Hayward N, Trent J; Lund Melanoma Study Group; Melanoma Genetics Consortium.
Localization of a novel melanoma susceptibility locus to 1p22.
Am J Hum Genet. 2003,73:301-13.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12844286

Pavel S, Smit NP, van der Meulen H, Kolb RM, de Groot AJ, van der Velden PA,Gruis NA, Bergman W.
Homozygous germline mutation of CDKN2A/p16 and glucose-6-phosphate dehydrogenase deficiency in a multiple melanoma case.
Melanoma Res. 2003,13:171-8.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12690301

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; Melanoma Genetics Consortium.
Geographical variation in the penetrance of CDKN2A mutations for melanoma.
J Natl Cancer Inst. 2002,94:894-903.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12072543

Brookes S, Rowe J, Ruas M, Llanos S, Clark PA, Lomax M, James MC, Vatcheva R, Bates S, Vousden KH, Parry D, Gruis N, Smit N, Bergman W, Peters G.
INK4a-deficient human diploid fibroblasts are resistant to RAS-induced senescence.
EMBO J. 2002,21:2936-45.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12065407

Kennedy C, Naipal A, Gruis NA, Struijk L, ter Schegget J, Willemze R, Claas FH, Bouwes Bavinck JN, Doxiadis II.
MICA gene polymorphism is not associated with an increased risk for skin cancer.
J Invest Dermatol. 2002,118:686-91.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11918717

Kennedy C, ter Huurne J, Berkhout M, Gruis N, Bastiaens M, Bergman W, Willemze R, Bavinck JN.
Melanocortin 1 receptor (MC1R) gene variants are associated with an increased risk for cutaneous melanoma which is largely independent of skin type and hair color.
J Invest Dermatol. 2001, 117:294-300.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11511307

van der Velden PA, Sandkuijl LA, Bergman W, Pavel S, van Mourik L, Frants RR, Gruis NA.
Melanocortin-1 receptor variant R151C modifies melanoma risk in Dutch families with melanoma.
Am J Hum Genet. 2001, 69:774-9.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11500806

Bastiaens M, ter Huurne J, Gruis N, Bergman W, Westendorp R, Vermeer BJ,Bouwes Bavinck JN.
The melanocortin-1-receptor gene is the major freckle gene.
Hum Mol Genet. 2001, 10:1701-8.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11487574

Metzelaar-Blok JA, ter Huurne JA, Hurks HM, Keunen JE, Jager MJ, Gruis NA.
Characterization of melanocortin-1 receptor gene variants in uveal melanoma patients.
Invest Ophthalmol Vis Sci. 2001, 42:1951-4.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11487574

van der Velden PA, Metzelaar-Blok JA, Bergman W, Monique H, Hurks H, Frants RR, Gruis NA, Jager MJ.
Promoter hypermethylation: a common cause of reduced p16(INK4a) expression in uveal melanoma.
Cancer Res. 2001, 61:5303-6.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11431374

Bastiaens MT, Struyk L, Tjong-A-Hung SP, Gruis N, ter Huurne J, Westendorp RG, Vermeer BJ, Bavinck JN, ter Schegget J.
Cutaneous squamous cell carcinoma and p53 codon 72 polymorphism: a need for screening?
Mol Carcinog. 2001, 30:56-61.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11255264

Bastiaens MT, ter Huurne JA, Kielich C, Gruis NA, Westendorp RG, Vermeer BJ, Bavinck JN; Leiden Skin Cancer Study Team.
Melanocortin-1 receptor gene variants determine the risk of nonmelanoma skin cancer independently of fair skin and red hair.
Am J Hum Genet. 2001, 68:884-94.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11254446

Gruis NA, Bergman W.
[From gene to disease; from p16 to melanoma].
Ned Tijdschr Geneeskd. 2000, 144:2100-2.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11103670

Vasen HF, Gruis NA, Frants RR, van Der Velden PA, Hille ET, Bergman W.
Risk of developing pancreatic cancer in families with familial atypical multiple mole melanoma associated with a specific 19 deletion of p16 (p16-Leiden).
Int J Cancer. 2000, 87:809-11.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10956390

Dekker SK, van Doorn R, Kempenaar J, Gruis NA, Vermeer BJ, Ponec M.
Skin equivalent: an attractive model to evaluate early melanoma metastasis.
Melanoma Res. 2000, 10:127-40.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10803713

Gruis NA, van der Velden PA, Bergman W, Frants RR.
Familial melanoma; CDKN2A and beyond.
J Investig Dermatol Symp Proc. 1999, 4:50-4. Review.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10537008

van der Velden PA, Sandkuijl LA, Bergman W, Hille ET, Frants RR, Gruis NA.
A locus linked to p16 modifies melanoma risk in Dutch familial atypical multiple mole melanoma (FAMMM) syndrome families.
Genome Res. 1999,9:575-80.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10400925

Snels DG, Hille ET, Gruis NA, Bergman W.
Risk of cutaneous malignant melanoma in patients with nonfamilial atypical nevi from a pigmented lesions clinic.
J Am Acad Dermatol. 1999, 40:686-93.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10321594

Latvian Biomedical Research and Study Centre

Our institution

Latvian Biomedical Research and Study Centre
Ratsupites 1
Riga LV-1067
Latvia

E-mail: zina@biomed.lu.lv


Our group

Laboratory of Melanoma Research
Latvian Biomedical Research and Study Centre
Ratsupites 1
Riga LV-1067
Latvia

Latvian Oncological Center
(Clinic)
Hipocrata 4
Riga LV-1038
Latvia


The Group leader

Olita Heisele, PhD
Latvian Biomedical Research and Study Centre
Ratsupites 1
Riga LV-1067
Latvia

E-mail: olita@biomed.lu.lv
Phone: 371-67808215
Fax: 371-67442407


Group description

Laboratory of Melanoma Research is focused on two main lines of research:
1) melanoma genetic and
2) melanoma immunogenetics and immunology

1. Recently the melanoma research group has focused on genetic background in melanoma development and we are registering melanoma families in Latvia. The group is involved in screening of melanoma susceptibility genes CDKN2A/ARF and CDK4 for their mutations. We have revealed two CDK4 R24H mutation positive families and follow up studies are going on. The group is involved in the analysis of the MC1R gene as a modifier of melanoma risk. We are collaborating with the Genome Database of Latvian Population and Latvian Oncological center.

2. Our melanoma immunogenetic studies are associated with the research on melanoma associated antigen (MAA) expression obtained in surgical samples. MAA profile of definite antigens (MAGE genes, MART, tyrosinaze, gp 100) was studied in accordance with clinical and histopathological features of tumour and patients surveillance.

3. The experimental study of MAA expression pattern in melanoma cell cultures after treatment with two different biomodulators elaborated in Latvia – Lariphan and Rigvir is carried out. Lariphan is double-stranded RNA of natural origin with interferon-inducing, antiviral, antitumoral effects. Rigvir is biomodulator of viral origin with immunomodulating, antitumoral and cytolytic effects.


Related Links

Latvian Biomedical Research and Study Centre
http://bmc.biomed.lu.lv.


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

Scientific team leader

Olita Heisele, PhD
olita@biomed.lu.lv

Clinical team leader

Ludmila Engele, PhD
ludmila.engele@gmail.com

Experienced Researchers

Dace Pjanova
dace@biomed.lu.lv

Baiba Streinerte, LOC
baiba.streinerte@aslimnica.lv

Dermatologist

Kristine Azariana

Technicians

Ingrida Desjatnikova, BMC (nurse)
ingrida@biomed.lu.lv

Vesma Matroze, LOC (nurse)

Student

Aija Ozola


Publications

Pjanova D, Heisele O, Engele L, Randerson-Moor JA, Harland M, Bishop DT, Newton Bishop JA, Taylor C, Debniak T, Lubinski J, Kleina R.
CDKN2A and CDK4 variants in Latvian melanoma patients: analysis of a clinic-based population.
Melanoma Res. 2007; 17 (3): 185-192.

Pjanova D, Heisele O, Engele L, Randerson-Moor JA, Kukalizch K, Bishop DT, Newton Bishop JA.
Analysis of Latvian melanoma families for 9p21 germline deletions by multiplex ligation-dependent probe amplification approach.
Acta Universitatis Latviensis. 2006; 710: 7-16.

Pjanova D, Engele L, Ignatovica V and Heisele O.
CDKN2A mutations and loss of heterozygosity in primary melanomas.
Proc. Latvian Acad. Sci. Section B. 2006; 60 (2/3): 98-100.

Pjanova D, Heisele O, Engele L, Desjatnikova I.
Tumour suppressor gene CDKN2A/p16 germline mutations in melanoma patients with additional cancer and cancer in their family history.
Acta Universitatis Latviensis. 2003, 662: 25-32.

Heisele O, Ferdats A, Engele L, Rupais A, Desjatnikova I.
Melanoma associated antigens as markers for melanoma progression and efficiacy of immunotherapy.
J.Tumour Marker Oncology. 2000, 15: 147-153.

Heisele O, Ferdats A, Engele L.
Melanoma associated antigens as additional markers of tumour progression.
J.Tumour Marker Oncology, 2000, 15: 147-153.

Pjanova D, Heisele O, Engele L, Balkovska I, Desjatnikova I, Ignatovica V.
CDKN2A/ARF and CDK4 germline alterations in sporadic cutaneous malignant melanoma patients of Latvian population.
In press.

Click here to see a PDF of this publication

GenoMEL (Latin America)

Coordinator

Dr Francisco Cuellar
facuellar@yahoo.com

Supervisor

Dr Susana Puig
spuig@clinic.ub.es


For the past three years we have been identifying cases of familial melanoma and multiple primary melanoma in Latin America. Both data and samples have been gathered for use in studies of CDKN2A (p16/p14ARF), CDK4 and MC1R at the Molecular Genetics Laboratory (MGL) of the Hospital Clnic of Barcelona (HCB).

This work is ongoing and we are anticipating a series of publications in 2009/2010.


Leaders in participant countries

Argentina

Dr Horacio Cabo
hcabo@sad.org.ar

Brazil

Dr Gilles Landman
glandman@terra.com.br

Chile

Dr Enrique Morales and Dr Claudia Balestrini
claubal@vtr.net

 Colombia

Dr Cesar Merlano
merlano@col.net.co

Mexico

Dr Blanca Carlos and Julio Salas
blancarlos_1@hotmail.com
jsalas@fm.uanl.mx

Uruguay

Dr Alejandra Larre-Borges
alarreborges@gmail.com


Presentations (a brief selection)

Genetic risk factors for melanoma development in Latin America
Presented at the 16th European Academy of Dermatology and Venereology (EADV) Congress, Vienna, Austria, May 2007 and the 20th World Congress of Dermatology, Buenos Aires, Argentina, October 2007.

Report of a novel CDKN2A germ line mutation in two melanoma prone families from Uruguay
Presented at the 21st World Congress of Dermatology, Buenos Aires, Argentina, October 2007. This work received an award as one of the top three poster presentations.

Interview about GenoMEL project
Presented on the Uruguayan TV show: “Calidad de Vida”. (Dr. Larre-Borges, Montevideo, Uruguay, December 2008).

NE Italy Melanoma Families Group

Our institution

National Cancer Institute


Our group

North Eastern Italy Melanoma Families Group
Genetic Epidemiology Branch
Division of Cancer Epidemiology and Genetics
National Cancer Institute
NIH/DHHS
Executive Plaza South
6120 Executive Blvd., Room 7114
Bethesda, MD 20892-7236
USA


The Group leader

Maria Teresa Landi, M.D., Ph.D.
Genetic Epidemiology Branch
Division of Cancer Epidemiology and Genetics
National Cancer Institute
NIH/DHHS
Executive Plaza South
6120 Executive Blvd., Room 7114
Bethesda, MD 20892-7236
USA

Tele: 01-301-402-9519
Fax: 01-301-402-4489
Email: landim@mail.nih.gov


We initiated a genetic epidemiologic study of familial melanoma in Cesena, Italy in 1994, in the North Eastern area of Italy. The major goal of the study is to investigate the genetic and environmental determinants of melanoma, in families with 2 or more relatives with melanoma. Multiple primary melanoma, dysplastic nevi, and pancreatic cancer cases are present in several families.

For families with no mutations in the CDKN2A gene, we search for additional susceptibility loci for melanoma. In addition, we study the contribution of modifier genes, including those involved in pigmentation, immune regulation, and DNA repair, and their interaction with environmental factors in the genesis of melanoma. Patients are evaluated at the Maurizio Bufalini Hospital of Cesena, Italy. The team currently include genetic epidemiologists, physicians, technicians, and laboratory investigators.


Related Links

National Cancer Institute
http://cancer.gov/

Genetic Epidemiology Branch
http://dceg.cancer.gov/genetic.html


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

Principal researchers

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

Alisa Goldstein, PhD
goldstea@mail.nih.gov

Margaret Tucker, MD
tuckerp@mail.nih.gov

Donato Calista
calista@iol.it

 

Labratory Scientists

Shirley Tsang, PhD
st248s@nih.gov

David Munroe, PhD
dm368n@nih.gov

 

Postdoctoral Fellow

Kimberly Kerstann, PhD
kkerstan@mail.nih.gov

 

Technicians

Paola Minghetti, MS
pminghetti@ausl-cesena.emr.it