CANCER GENOMICS

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​A comparative molecular analysis of esophageal, gastric and colorectal adenocarcinomas revealed several key findings: 

• Chromosomal instability tumors are the most common, heterogenous molecular subtype enriched in the anatomical extremes of the gastrointestinal tract

• Unlike colorectal cancer, gastric and esophageal cancer exhibit marked genome fragmentation with a high density of focal amplifications

• ​Following TP53 mutations, oncogenic pathways tend to be activated by amplifications rather than mutations in the upper GI tract
  

• MSI tumors showed a robust IFN-ɣ signature whereas SNV-predominant hypermutated tumors demonstrated NK-cell activity

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We identified a previously unrecognized subtype of colorectal cancer that lacks hypermutation and significant aneuploidy known as genome stable.  A striking feature of this subtype is recurrent mutations in the transcription factor SOX9.  The lab is focused on defining the clinical and functional significance of SOX9 mutations using genetically engineered mouse models, organoid systems, and single-cell transcriptomics.

Duronio et al., Gastro Hep Advances, 2022