Recurrent genomic regions of focal copy number alteration in clinically aggressive endometrial carcinomas

Monday, October 24, 2011 — Poster Session I
Noon – 2:00 p.m.	Natcher Conference Center	NHGRI	CANCER-17

Authors

• AJ O’Hara
• ML Rudd
• M Le Gallo
• CL Hanigan
• MJ Merino
• B Borate
• T Wolfsberg
• LC Brody
• SC Chandrasekharappa
• DW Bell

Abstract

Non-endometrioid endometrial carcinomas (NEECs) are the most clinically aggressive subtype of endometrial cancer. Most NEECs are aneuploid, but there is little information on the underlying copy number alterations (CNAs). We used high-resolution, SNP-based, whole genome genotyping to comprehensively catalog somatic changes in copy number within a series of primary NEECs. Among 43 NEECs profiled, 33 (77%) had one or more focal CNAs. Overall, we identified 288 somatic CNAs encompassing 1441 protein-encoding genes and 45 miRNAs. We searched for recurrent CNAs and found 26 recurrent regions of high-copy gain (≥6 copies) and five recurrent regions of homozygous deletion. Pathway enrichment analysis of the recurrently altered genes revealed the ERBB signaling pathway to be altered at high statistical significance. In parallel sequencing studies, we observed somatic mutations within the ERBB signaling pathway in 33% of NEECs. By integrating our copy number data and mutational data, 45% of NEECs investigated had one or more alterations in the ERBB pathway. In summary, this represents one of the most comprehensive studies of CNA in NEECs. Future studies will integrate our CNA dataset with comprehensive catalogs of somatic mutations and expression changes in NEEC to identify causal cancer genes that contribute to this aggressive malignancy.

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