Hereditary ovarian cancer: not only BRCA 1 and 2 genes

Biomed Res Int. 2015:2015:341723. doi: 10.1155/2015/341723. Epub 2015 May 17.

Abstract

More than one-fifth of ovarian tumors have hereditary susceptibility and, in about 65-85% of these cases, the genetic abnormality is a germline mutation in BRCA genes. Nevertheless, several other suppressor genes and oncogenes have been associated with hereditary ovarian cancers, including the mismatch repair (MMR) genes in Lynch syndrome, the tumor suppressor gene, TP53, in the Li-Fraumeni syndrome, and several other genes involved in the double-strand breaks repair system, such as CHEK2, RAD51, BRIP1, and PALB2. The study of genetic discriminators and deregulated pathways involved in hereditary ovarian syndromes is relevant for the future development of molecular diagnostic strategies and targeted therapeutic approaches. The recent development and implementation of next-generation sequencing technologies have provided the opportunity to simultaneously analyze multiple cancer susceptibility genes, reduce the delay and costs, and optimize the molecular diagnosis of hereditary tumors. Particularly, the identification of mutations in ovarian cancer susceptibility genes in healthy women may result in a more personalized cancer risk management with tailored clinical and radiological surveillance, chemopreventive approaches, and/or prophylactic surgeries. On the other hand, for ovarian cancer patients, the identification of mutations may provide potential targets for biologic agents and guide treatment decision-making.

Publication types

  • Review

MeSH terms

  • BRCA1 Protein* / genetics
  • BRCA1 Protein* / metabolism
  • BRCA2 Protein* / genetics
  • BRCA2 Protein* / metabolism
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics
  • Colorectal Neoplasms, Hereditary Nonpolyposis / metabolism
  • Colorectal Neoplasms, Hereditary Nonpolyposis / pathology
  • Colorectal Neoplasms, Hereditary Nonpolyposis / therapy
  • DNA Mismatch Repair*
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Li-Fraumeni Syndrome / genetics
  • Li-Fraumeni Syndrome / metabolism
  • Li-Fraumeni Syndrome / pathology
  • Li-Fraumeni Syndrome / therapy
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / metabolism
  • Ovarian Neoplasms* / pathology
  • Ovarian Neoplasms* / therapy

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human