title: BRCA1 mutation site may be linked with nuclear DNA ploidy in BRCA1-mutated ovarian carcinomas.
abstract: OBJECTIVE
  BRCA1 has a role in maintaining normal nuclear DNA content during cell division and its inactivation may result in DNA aneuploidy and cancer progression. BRCA1-linked breast cancers are more aneuploid and have a worse prognosis, but this has not been elucidated in ovarian cancers. This study explores the potential difference in ploidy status between BRCA1-mutated and sporadic ovarian carcinomas. It also explores the potential association between BRCA1 mutation site and DNA ploidy status.
  
  
  METHODS
  This study compared DNA ploidy status of tumor blocks from 23 BRCA1-mutated ovarian carcinomas with that of 23 sporadic ovarian carcinomas matched for histologic subtype, patient age, stage and grade. DNA content of the nuclei was measured by Feulgen-Schiff staining followed by image cytometry and compared.
  
  
  RESULTS
  BRCA1-linked tumors with a stop codon closer to the N-terminal (between 1 and 500 aa; 6/6, 100%) had a significantly higher frequency of nondiploidy compared with those with stop codon above 500 aa (7/12, 58%) (P = 0.033). A diploid peak was detected in 28% of BRCA1-mutated ovarian cancers and in 33% of sporadic ovarian cancers.
  
  
  CONCLUSIONS
  The present study concluded that ovarian tumors with mutations closer to the N-terminal of BRCA1 may have a higher risk of DNA aneuploidy. There is no significant difference between BRCA1-mutated and sporadic ovarian carcinomas with respect to the DNA content.
authors.affiliation: Illawarra Cancer Care Centre, Wollongong Hospital, Wollongong, New South Wales, Australia; Peter MacCallum Cancer Centre, Research Division, The Kathleen Cuningham Consortium for Research into Familial Breast Cancer, East Melbourne, Victoria, Australia.
authors.forename: Morteza
authors.initials: M
authors.lastname: Aghmesheh
authors.forename: Akshat
authors.initials: A
authors.lastname: Saxena
authors.forename: Farshid
authors.initials: F
authors.lastname: Niknam
mesh_terms: D000782:Aneuploidy; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1 / Q000502:physiology*; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics*; D011003:Ploidies
chemical_list: D004273:DNA, Neoplasm
keywords: BRCA1; DNA content; aneuploidy; image cytometry; ovarian cancer; ploidy