title: The molecular genetics of hereditary and sporadic ovarian cancer: implications for the future.
abstract: BACKGROUND
  Epithelial ovarian cancer (EOC) is a heterogeneous condition with poor survival outcomes. The genetics of hereditary and sporadic ovarian cancers will be covered and its implications to management and future research are discussed.
  
  
  METHODS
  Key recent published literature.
  
  
  RESULTS
  Both genetic and environmental factors play a role in the development of EOC. Most EOCs develop sporadically and are divided into low-grade/genetically stable type I tumours and high-grade/genetically unstable type II tumours. The commonest hereditary syndromes are hereditary breast ovarian cancer syndrome (HBOC-BRCA mutations) and Lynch syndrome (DNA mismatch repair mutations).
  
  
  RESULTS
  The different histological types of EOC may not solely originate from the ovary but from the fallopian tube and endometriosis deposits; there is increasing evidence to support this.
  
  
  CONCLUSIONS
  Our understanding of the genetics and frequencies of mutations in ovarian cancer is expanding. The proportion of heritable EOC is larger than previously estimated and not all patients have a clear family history for this. Mutations in genes involving the downstream BRCA signalling pathway have recently been implicated in HBOC. TP53 mutations are the single most commonly identified mutations in aggressive sporadic high-grade serous carcinomas, affecting essentially 100% of such tumours. Furthermore, there is increasing recognition that the different histological sub-types need to be treated as separate entities.
  
  
  CONCLUSIONS
  Given how heterogeneous 'ovarian' cancer is, trials into new drugs should report responses for the different histo-/geno-types rather than simply using staging. Although the effect of new drugs such as poly(ADP-ribose) polymerase inhibitors are being investigated in ovarian cancer, there is still a need to develop targeted therapies-especially to tackle mutations in PI3 K pathway, RAS pathway and TP53.
authors.affiliation: Ovarian Cancer Action Research Centre, Department of Surgery and Cancer, Imperial College London, Du Cane Road, London W12 0NN, UK.
authors.forename: Maise
authors.initials: M
authors.lastname: Al Bakir
authors.affiliation: Ovarian Cancer Action Research Centre, Department of Surgery and Cancer, Imperial College London, Du Cane Road, London W12 0NN, UK h.gabra@imperial.ac.uk.
authors.forename: Hani
authors.initials: H
authors.lastname: Gabra
mesh_terms: D000077216:Carcinoma, Ovarian Epithelial; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D020022:Genetic Predisposition to Disease; D061325:Hereditary Breast and Ovarian Cancer Syndrome / Q000235:genetics; D006801:Humans; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000628:therapy; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000628:therapy; D057285:Precision Medicine / Q000379:methods; D012307:Risk Factors
keywords: genetics; hereditary; management; origins; ovarian cancer; sporadic