Methylation profiles of hereditary and sporadic ovarian cancer.
OBJECTIVE
Tumour suppressor gene silencing through promoter hypermethylation plays an important role in oncogenesis. Carcinogenesis of hereditary cancers usually differs from that of their sporadic counterparts, but methylation has hardly been studied in hereditary ovarian cancer. The aim of this study was to investigate promoter methylation of a set of common tumour suppressor genes in BRCA1-related ovarian cancer in comparison with sporadic ovarian cancer.


RESULTS
Methylation-specific multiplex ligation-dependent probe amplification was used to assess the extent of promoter methylation of 24 different tumour suppressor genes in BRCA1-associated (n = 25) and matched sporadic ovarian tumours (n = 50). A cumulative methylation index (CMI) was calculated and differences between individual genes were analysed. There was no significant difference in cumulative methylation between BRCA1-associated and sporadic ovarian carcinomas (median CMI 108; CMI 110; P = 0.86). Also, methylation patterns of individual genes did not show distinct differences after correction for multiple comparisons. CDH13, GSTP1 and RASSF1 were frequently methylated in both sporadic and hereditary ovarian cancers. BRCA1 methylation occurred in 14% of sporadic tumours, but was not detected in BRCA1-associated tumours.


CONCLUSIONS
CDH13, GSTP1 and RASSF1 are frequently methylated in both sporadic and BRCA1-associated ovarian cancers. Interestingly, methylation of BRCA1, while frequent in sporadic ovarian cancer, never occurred in the hereditary group. BRCA1-associated ovarian cancers mimic their sporadic counterparts in extent and pattern of promoter methylation of several common tumour suppressor genes. This finding could have implications for future chemotherapy regimens based on epigenetic changes.
Bol
Guus M
GM
Department of Pathology, University Medical Centre Utrecht Cancer Centre, Utrecht, the Netherlands.
Suijkerbuijk
Karijn P M
KP
Bart
Joost
J
Vooijs
Marc
M
van der Wall
Elsken
E
van Diest
Paul J
PJ
D000328:Adult; D000368:Aged; D015820:Cadherins / Q000235:genetics; D019175:DNA Methylation; D057890:Epigenomics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019398:Genes, BRCA1; D051549:Glutathione S-Transferase pi / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics
D015820:Cadherins; C099972:H-cadherin; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi