title: Targeted mutation analysis of endometrial clear cell carcinoma.
abstract: OBJECTIVE
  Endometrial clear cell carcinomas (CCC) constitute fewer than 5% of all carcinomas of the endometrium. Currently, little is known regarding the genetic basis of endometrial CCC.
  
  
  RESULTS
  We performed genomic and immunohistochemical analyses on 14 rigorously reviewed pure endometrial CCC. The genomic analysis consisted of sequencing the coding regions of 26 genes implicated previously in endometrial carcinoma. Twelve of 14 tumours displayed a prototypical CCC immunophenotype [napsin A+, hepatocyte nuclear factor-1β (HNF1β(+) ) and oestrogen receptor(-) ] and all showed intact mismatch repair protein expression. We detected mutations in 11 of 14 tumours, and there was a predominance of mutations involving genes that are mutated more frequently in endometrial serous carcinomas than in endometrioid carcinomas. Two tumours displayed a prototypical serous carcinoma mutation profile (concurrent TP53 and PPP2R1A mutations, without PTEN, CTNNB1 or ARID1A mutation). No mutations in PTEN, CTNNB1 or POLE were identified.
  
  
  CONCLUSIONS
  The overall mutation profile of this cohort of endometrial CCC appears to be more serous-like than endometrioid-like, with a minor subset in the TP53-mutated CCC showing serous carcinoma profile. These findings provide new insights into the molecular features of morphologically prototypical endometrial CCC, and underscore the need for further investigations into the oncogenesis of endometrial CCC.
authors.affiliation: Department of Pathology and Laboratory Medicine, Genetic Pathology Evaluation Center, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Lien N
authors.initials: LN
authors.lastname: Hoang
authors.forename: Melissa K
authors.initials: MK
authors.lastname: McConechy
authors.forename: Bo
authors.initials: B
authors.lastname: Meng
authors.forename: John B
authors.initials: JB
authors.lastname: McIntyre
authors.forename: Carol
authors.initials: C
authors.lastname: Ewanowich
authors.forename: Cyril Blake
authors.initials: CB
authors.lastname: Gilks
authors.forename: David G
authors.initials: DG
authors.lastname: Huntsman
authors.forename: Martin
authors.initials: M
authors.lastname: Köbel
authors.forename: Cheng-Han
authors.initials: CH
authors.lastname: Lee
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000235:genetics* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics; D054648:Protein Phosphatase 2 / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; C517191:PPP2R1A protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D054648:Protein Phosphatase 2
keywords: TP53; clear cell carcinoma; endometrial cancer; next generation sequencing