title: Ovarian and endometrial endometrioid carcinomas have distinct CTNNB1 and PTEN mutation profiles.
abstract: Ovarian endometrioid carcinomas and endometrial endometrioid carcinomas share many histological and molecular alterations. These similarities are likely due to a common endometrial epithelial precursor cell of origin, with most ovarian endometrioid carcinomas arising from endometriosis. To directly compare the mutation profiles of two morphologically similar tumor types, endometrial endometrioid carcinomas (n=307) and ovarian endometrioid carcinomas (n=33), we performed select exon capture sequencing on a panel of genes: ARID1A, PTEN, PIK3CA, KRAS, CTNNB1, PPP2R1A, TP53. We found that PTEN mutations are more frequent in low-grade endometrial endometrioid carcinomas (67%) compared with low-grade ovarian endometrioid carcinomas (17%) (P<0.0001). By contrast, CTNNB1 mutations are significantly different in low-grade ovarian endometrioid carcinomas (53%) compared with low-grade endometrial endometrioid carcinomas (28%) (P<0.0057). This difference in CTNNB1 mutation frequency may be reflective of the distinct microenvironments; the epithelial cells lining an endometriotic cyst within the ovary are exposed to a highly oxidative environment that promotes tumorigenesis. Understanding the distinct mutation patterns found in the PI3K and Wnt pathways of ovarian and endometrial endometrioid carcinomas may provide future opportunities for stratifying patients for targeted therapeutics.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, BC Cancer Agency, Centre for Translational and Applied Genomics, Vancouver, BC, Canada.
authors.forename: Melissa K
authors.initials: MK
authors.lastname: McConechy
authors.affiliation: 1] Department of Molecular Oncology, BC Cancer Agency, Vancouver, BC, Canada [2] Department of Computer Science, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Jiarui
authors.initials: J
authors.lastname: Ding
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, BC Cancer Agency, Centre for Translational and Applied Genomics, Vancouver, BC, Canada.
authors.forename: Janine
authors.initials: J
authors.lastname: Senz
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, BC Cancer Agency, Centre for Translational and Applied Genomics, Vancouver, BC, Canada.
authors.forename: Winnie
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, BC Cancer Agency, Centre for Translational and Applied Genomics, Vancouver, BC, Canada.
authors.forename: Nataliya
authors.initials: N
authors.lastname: Melnyk
authors.affiliation: Division of Gynecology Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada.
authors.forename: Alicia A
authors.initials: AA
authors.lastname: Tone
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, BC Cancer Agency, Centre for Translational and Applied Genomics, Vancouver, BC, Canada.
authors.forename: Leah M
authors.initials: LM
authors.lastname: Prentice
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, BC Cancer Agency, Centre for Translational and Applied Genomics, Vancouver, BC, Canada.
authors.forename: Kimberly C
authors.initials: KC
authors.lastname: Wiegand
authors.affiliation: Division of Gynaecologic Oncology, Department of Obstetrics and Gynaecology, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Jessica N
authors.initials: JN
authors.lastname: McAlpine
authors.affiliation: 1] Department of Molecular Oncology, BC Cancer Agency, Vancouver, BC, Canada [2] Department of Computer Science, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Sohrab P
authors.initials: SP
authors.lastname: Shah
authors.affiliation: Department of Pathology and Laboratory Medicine, Vancouver General Hospital and University of British Columbia, Vancouver, BC, Canada.
authors.forename: Cheng-Han
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, Ohio State University, Columbus, OH, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Goodfellow
authors.affiliation: Department of Pathology and Laboratory Medicine, Vancouver General Hospital and University of British Columbia, Vancouver, BC, Canada.
authors.forename: C Blake
authors.initials: CB
authors.lastname: Gilks
authors.affiliation: 1] Department of Pathology and Laboratory Medicine, University of British Columbia, BC Cancer Agency, Centre for Translational and Applied Genomics, Vancouver, BC, Canada [2] Department of Molecular Oncology, BC Cancer Agency, Vancouver, BC, Canada.
authors.forename: David G
authors.initials: DG
authors.lastname: Huntsman
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D018269:Carcinoma, Endometrioid / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D060787:Neoplasm Grading; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D010641:Phenotype; D059016:Tumor Microenvironment; D051176:beta Catenin / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D051176:beta Catenin; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human