Hereditary ovarian carcinoma: Heterogeneity, molecular genetics, pathology, and management

• Published in: Molecular oncology Vol. 3; no. 2; pp. 97 - 137
• Main Authors: Lynch, Henry T., Casey, Murray Joseph, Snyder, Carrie L., Bewtra, Chhanda, Lynch, Jane F., Butts, Matthew, Godwin, Andrew K.
• Format: Journal Article
• Language: English
• Published: United States Elsevier B.V 01.04.2009; John Wiley & Sons, Inc; John Wiley and Sons Inc
• Subjects: Adaptor Proteins, Signal Transducing - genetics; BRCA1 protein; BRCA2 protein; Breast; Breast cancer; Breast Neoplasms - genetics; Female; Genes, BRCA1; Genes, BRCA2; Genetic Predisposition to Disease; Hereditary breast-ovarian cancer syndrome; Hereditary ovarian cancer; Humans; Lynch syndrome; Lynch Syndrome II - genetics; Malignancy; Mismatch repair; MLH1 protein; MSH2 protein; Mutation; MutL Protein Homolog 1; MutS Homolog 2 Protein - genetics; Neoplastic Syndromes, Hereditary - genetics; Nuclear Proteins - genetics; Ovarian cancer; Ovarian carcinoma; Ovarian Neoplasms - genetics; Review; Thematic Issue Reviews; United States > US; Hereditary ovarian cancer; Review; Hereditary breast-ovarian cancer syndrome; Ovarian cancer; Lynch syndrome
• ISSN: 1574-7891; 1878-0261; 1878-0261
• DOI: 10.1016/j.molonc.2009.02.004

Hereditary ovarian cancer accounts for at least 5% of the estimated 22,000 new cases of this disease during 2009. During this same time, over 15,000 will die from malignancy ascribed to ovarian origin. The bulk of these hereditary cases fits the hereditary breast–ovarian cancer syndrome, while virtually all of the remainder will be consonant with the Lynch syndrome, disorders which are autosomal dominantly inherited. Advances in molecular genetics have led to the identification of BRCA1 and BRCA2 gene mutations which predispose to the hereditary breast–ovarian cancer syndrome, and mutations in mismatch repair genes, the most common of which are MSH2 and MLH1, which predispose to Lynch syndrome. These discoveries enable relatively certain diagnosis, limited only by their variable penetrance, so that identification of mutation carriers through a comprehensive cancer family history might be possible. This paper reviews the subject of hereditary ovarian cancer, with particular attention to its molecular genetic basis, its pathology, and its phenotypic/genotypic heterogeneity.