Comprehensive genomic and transcriptomic characterization of small bowel adenocarcinoma


Karan Pandya, Joanne Xiu, Alex Farrell, Michael J. Overman, Andreas Seeber, Jim Abraham, Anthony Frank Shields, Emil Lou, John Marshall, James L. Abbruzzese, Heinz-Josef Lenz, Wolfgang Michael Korn, Pat Gulhati

Key Findings: 

  • Analysis of 823 small bowel tumor samples with DNA and RNA sequencing represents the largest molecular profile study to date of this rare cancer type. 
  • Subsites of small bowel tumors were shown to present distinct molecular features, suggesting differential treatment opportunities. 
  • Different subsites were also enriched for targetable alterations, including HER2 overexpression and ERBB2 amplification in duodenal; RSPO3 fusions and BRAF and ERBB2 (HER2) mutations in jejunal; and mutations in genes encoding DNA damage repair proteins in ileal small bowel adenocarcinomas. 
  • Comparison with a large cohort of colorectal cancer samples revealed dramatically different molecular landscapes, tumor microenvironment characteristics, and clinical outcomes, justifying the recent addition of small bowel adenocarcinoma-specific guidelines to clinical practice and highlighting the need for molecular profiling to inform cancer therapy. 
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