title: Gene expression profiles of BRCA1-linked, BRCA2-linked, and sporadic ovarian cancers.
abstract: BACKGROUND
  Germline mutations in BRCA1 and BRCA2 are responsible for 5%-10% of epithelial ovarian cancers, but the molecular pathways affected by these mutations are unknown. We used complementary DNA (cDNA) microarrays to compare gene expression patterns in ovarian cancers associated with BRCA1 or BRCA2 mutations with gene expression patterns in sporadic epithelial ovarian cancers and to identify patterns common to both hereditary and sporadic tumors.
  
  
  METHODS
  Tumor samples from 61 patients with pathologically confirmed epithelial ovarian adenocarcinoma with matched clinicopathologic features were studied, including 18 with BRCA1 founder mutations, 16 with BRCA2 founder mutations, and 27 without either founder mutation (termed sporadic cancers). The cDNA microarrays contained 7651 sequence-verified features. Gene expression data were analyzed with a modified two-sided F test, with P<.0001 considered statistically significant. The expression level of six genes was also studied with reverse transcription-polymerase chain reaction.
  
  
  RESULTS
  The greatest contrast in gene expression was observed between tumors with BRCA1 mutations and those with BRCA2 mutations; 110 genes showed statistically significantly different expression levels (P<.0001). This group of genes could segregate sporadic tumors into two subgroups, "BRCA1-like" and "BRCA2-like," suggesting that BRCA1-related and BRCA2-related pathways are also involved in sporadic ovarian cancers. Fifty-three genes were differentially expressed between tumors with BRCA1 mutations and sporadic tumors; six of the 53 mapped to Xp11.23 and were expressed at higher levels in tumors with BRCA1 mutations than in sporadic tumors. Compared with the immortalized ovarian surface epithelial cells used as reference, several interferon-inducible genes were overexpressed in the majority of tumors with a BRCA mutation and in sporadic tumors.
  
  
  CONCLUSIONS
  Mutations in BRCA1 and BRCA2 may lead to carcinogenesis through distinct molecular pathways that also appear to be involved in sporadic cancers. Sporadic carcinogenic pathways may result from epigenetic aberrations of BRCA1 and BRCA2 or their downstream effectors.
authors.affiliation: Division of Clinical Sciences of the National Cancer Institute, Gaithersburg, MD,USA.
authors.forename: Amir A
authors.initials: AA
authors.lastname: Jazaeri
authors.forename: Cindy J
authors.initials: CJ
authors.lastname: Yee
authors.forename: Christos
authors.initials: C
authors.lastname: Sotiriou
authors.forename: Kelly R
authors.initials: KR
authors.lastname: Brantley
authors.forename: Jeff
authors.initials: J
authors.lastname: Boyd
authors.forename: Edison T
authors.initials: ET
authors.lastname: Liu
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000235:genetics* / Q000378:metabolism; D002288:Adenocarcinoma, Mucinous / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D018269:Carcinoma, Endometrioid / Q000235:genetics* / Q000378:metabolism; D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D017931:DNA Primers; D012333:RNA, Messenger; D012334:RNA, Neoplasm