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The molecular basis of ovarian cancer
Author(s) -
Gallion Holly H.,
Pieretti Maura,
Depriest Paul D.,
Van Nagell J. R.
Publication year - 1995
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19951115)76:10+<1992::aid-cncr2820761315>3.0.co;2-u
Subject(s) - ovarian cancer , loss of heterozygosity , tumor suppressor gene , carcinogenesis , cancer research , oncogene , ovary , cancer , colorectal cancer , biology , ovarian tumor , gene , medicine , pathology , allele , genetics , cell cycle
Background . Molecular genetic studies of ovarian cancer have been limited by the inaccessible location of the ovary, the advanced stage of tumors available for analysis, and the lack of a well‐defined precursor lesion. However, genetic alterations important in ovarian tumorigenesis have been identified recently. Methods . Molecular genetic evaluation of ovarian cancer primarily has utilized mutation analysis, immunohistochemical techniques, and loss of heterozygosity (LOH) studies. Results . Overexpression of the HER‐2/ neu oncogene is present in approximately one third of ovarian cancers and is associated with poor prognosis. Mutations of the K‐ ras oncogene have been identified in a similar proportion of mucinous ovarian tumors, including borderline tumors. The study authors as well as others have frequently detected LOH on chromosome 17, including the p53 and BRCA1 loci, and at 17p3.3 and 1717q22‐23. Genetic linkage analysis indicates that the majority of inherited ovarian cancers are caused by mutations in the BRCA1 gene. Mutations in mismatch repair genes have been identified in ovarian cancers that occur as part of the hereditary nonpolyposis colon cancer syndrome. Conclusions . Sporadic ovarian tumors are the end result of a complex pathway involving multiple oncogenes and tumor suppressor genes, including HER‐2/ neu , K‐ ras , p53, BRCA1 , and additional tumor suppressor genes on chromosome 17. The majority of inherited ovarian cancers are due to mutations in the BRCA1 gene, which appears to be a tumor suppressor gene. It is hoped that an increased understanding of the molecular basis of ovarian cancer will lead to advances in prevention, diagnosis, and treatment. Cancer 1995; 76:1992–7.