ORIGINAL ARTICLE

Molecular evidence for putative tumour suppressor genes on chromosome 13q specific to BRCA1 related ovarian and fallopian tube cancer

A P M Jongsma¹, J M J Piek¹, R P Zweemer¹, R H M Verheijen¹, J W T Klein Gebbinck¹, G J van Kamp², I J Jacobs⁴, P Shaw⁵, P J van Diest³ and P Kenemans¹

¹ Department of Obstetrics and Gynaecology, 1007 MB, Amsterdam, The Netherlands
² Department of Clinical Chemistry, VU University Medical Center
³ Department of Pathology, VU University Medical Center
⁴ Gynaecology Cancer Research Unit, St Bartholomew’s Hospital, London EC1 7BE, UK
⁵ Division of Anatomical Pathology, Sunnybrook Health Sciences Centre, University of Toronto, M4N3M5 Canada

Correspondence to:
Correspondence to:
Professor P J van Diest, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands;
pj.vandiest{at}vumc.nl

Background/Aims: Loss of heterozygosity (LOH) on chromosome 13q has been reported to occur frequently in human ovarian cancer, and indications have been found that chromosome 13 may also play a specific role in the inherited form of ovarian cancer. The aim of this study was to define regions on chromosome 13 that may harbour additional tumour suppressor genes involved in the tumorigenesis of BRCA1 related ovarian and fallopian tube cancer.

Materials/methods: DNA extracted from paraffin wax blocks of 36 BRCA1 associated ovarian and fallopian tube carcinomas was analysed by LOH polymerase chain reaction using seven highly polymorphic microsatellite markers spanning chromosome 13q.

Results: High LOH frequencies were found on loci 13q11, 13q14, 13q21, 13q22–31, 13q32, and 13q32–4, suggesting the presence of putative tumour suppressor genes on the long arm of chromosome 13 that may play a role in the pathogenesis of BRCA1 related ovarian and fallopian tube cancer. LOH patterns appeared to be independent of the type of BRCA1 mutation, stage, and grade. Although in some cases there were indications for loss of larger parts of chromosome 13, in most cases losses were fairly randomly distributed over chromosome 13 with retained parts in between lost parts. Microsatellite instability was found in six cases.

Conclusion: Several loci on chromosome 13q show high frequencies of LOH in BRCA1 related ovarian and fallopian tube cancer, and may therefore harbour putative tumour suppressor genes involved in the carcinogenesis of this particular type of hereditary cancer.

Keywords: BRCA1; loss of heterozygosity; ovarian carcinoma; fallopian tube carcinoma

Abbreviations: CGH, comparative genomic hybridisation; LOH, loss of heterozygosity; MSI, microsatellite instability; PCR, polymerase chain reaction; RB1, retinoblastoma gene

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