ARID1A mutations in endometriosis-associated ovarian carcinomas
- Kimberly C Wiegand 1, Sohrab P Shah , Osama M Al-Agha , Yongjun Zhao , Kane Tse , Thomas Zeng , Janine Senz , Melissa K McConechy , Michael S Anglesio , Steve E Kalloger , Winnie Yang , Alireza Heravi-Moussavi , Ryan Giuliany , Christine Chow , John Fee , Abdalnasser Zayed , Leah Prentice , Nataliya Melnyk , Gulisa Turashvili , Allen D Delaney , Jason Madore , Stephen Yip , Andrew W McPherson , Gavin Ha , Lynda Bell , Sian Fereday , Angela Tam , Laura Galletta , Patricia N Tonin , Diane Provencher , Dianne Miller , Steven J M Jones , Richard A Moore , Gregg B Morin , Arusha Oloumi , Niki Boyd , Samuel A Aparicio , Ie-Ming Shih , Anne-Marie Mes-Masson , David D Bowtell , Martin Hirst , Blake Gilks , Marco A Marra , David G Huntsman
- 1British Columbia Cancer Agency, Vancouver, Canada.
- 0British Columbia Cancer Agency, Vancouver, Canada.
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View abstract on PubMed
Summary
This summary is machine-generated.Mutations in the ARID1A gene are common in ovarian clear-cell and endometrioid carcinomas, suggesting it acts as a tumor suppressor. These ARID1A gene alterations may be an early step in endometriosis transforming into cancer.
Area Of Science
- Gynecologic Oncology
- Cancer Genomics
- Tumorigenesis
Background
- Ovarian clear-cell and endometrioid carcinomas may originate from endometriosis.
- The molecular mechanisms driving this transformation remain largely undescribed.
Purpose Of The Study
- To investigate the molecular events, specifically mutations in the ARID1A gene, involved in the development of ovarian clear-cell and endometrioid carcinomas from endometriosis.
- To determine the frequency and significance of ARID1A mutations and BAF250a protein expression in different ovarian carcinoma subtypes.
Main Methods
- Whole transcriptome sequencing of ovarian clear-cell carcinomas and cell lines to identify somatic mutations.
- Targeted sequencing of the ARID1A gene in a larger cohort of ovarian carcinomas.
- Immunohistochemical analysis to assess BAF250a protein expression in ovarian carcinomas.
Main Results
- Somatic mutations in ARID1A were identified in 46% of ovarian clear-cell carcinomas and 30% of endometrioid carcinomas, but not in high-grade serous carcinomas.
- Loss of BAF250a protein expression strongly correlated with ARID1A mutations and these specific ovarian cancer subtypes.
- ARID1A mutations and BAF250a loss were observed in preneoplastic atypical endometriosis in two patients, suggesting an early role in tumorigenesis.
Conclusions
- ARID1A functions as a tumor suppressor gene frequently altered in ovarian clear-cell and endometrioid carcinomas.
- ARID1A mutations and subsequent BAF250a protein loss are likely early events in the malignant transformation of endometriosis.
- These findings provide critical insights into the pathogenesis of endometriosis-associated ovarian cancers.
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