Ovarian and endometrial endometrioid carcinomas have distinct CTNNB1 and PTEN mutation profiles

被引：183

作者：

McConechy, Melissa K. ^{[1
]}

Ding, Jiarui ^{[2
,3
]}

Senz, Janine ^{[1
]}

Yang, Winnie ^{[1
]}

Melnyk, Nataliya ^{[1
]}

Tone, Alicia A. ^{[4
]}

Prentice, Leah M. ^{[1
]}

Wiegand, Kimberly C. ^{[1
]}

McAlpine, Jessica N. ^{[5
]}

Shah, Sohrab P. ^{[2
,3
]}

Lee, Cheng-Han ^{[6
]}

Goodfellow, Paul J. ^{[8
]}

Gilks, C. Blake ^{[6
,7
]}

Huntsman, David G. ^{[1
,2
]}

机构：

[1] Univ British Columbia, Dept Pathol & Lab Med, BC Canc Agcy, Ctr Translat & Appl Genom, Vancouver, BC V5E 4E6, Canada

[2] BC Canc Agcy, Dept Mol Oncol, Vancouver, BC, Canada

[3] Univ British Columbia, Dept Comp Sci, Vancouver, BC V5E 4E6, Canada

[4] Princess Margaret Canc Ctr, Div Gynecol Oncol, Toronto, ON, Canada

[5] Univ British Columbia, Vancouver Gen Hosp, Dept Obstet & Gynaecol, Div Gynaecol Oncol, Vancouver, BC V5E 4E6, Canada

[6] Vancouver Gen Hosp, Dept Pathol & Lab Med, Vancouver, BC V5Z 14E3, Canada

[7] Univ British Columbia, Vancouver, BC V5E 4E6, Canada

[8] Ohio State Univ, Coll Med, Dept Obstet & Gynecol, Columbus, OH 43210 USA

来源：

MODERN PATHOLOGY | 2014年 / 27卷 / 01期

基金：

加拿大健康研究院;

关键词：

carcinoma; CTNNB1; endometrial; endometrioid; mutations; ovarian; PTEN; BETA-CATENIN GENE; CLEAR-CELL CARCINOMA; HIGH-FREQUENCY; MICROSATELLITE INSTABILITY; MOLECULAR PATHOGENESIS; EXPRESSION PATTERN; SOMATIC MUTATIONS; STAGE-I; CANCER; PATHWAY;

D O I：

10.1038/modpathol.2013.107

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

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.

引用

页码：128 / 134

页数：7

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