Targeted mutational analysis of inflammatory bowel disease–associated colorectal cancers

Lindsay Alpert*, Lindsay Yassan, Rachel Poon, Sabah Kadri, Nifang Niu, Sushant A. Patil, Ibro Mujacic, David Montes, Filippo Galbo, Michelle N. Wurst, Chao Jie Zhen, Russell D. Cohen, David T. Rubin, Joel R. Pekow, Christopher R. Weber, Shu Yuan Xiao, John Hart, Jeremy Segal, Namrata Setia

*Corresponding author for this work

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Inflammatory bowel disease–associated colorectal carcinomas (IBD-CRCs)develop in a background of chronic inflammation, and thus, the molecular landscape of these tumors likely differs from that of sporadic colorectal cancer. To add to emerging data on molecular alterations present in these tumors, we analyzed our institution's cohort of IBD-CRCs. CRCs resected from patients with IBD underwent molecular analysis via a 50-gene hot-spot solid tumor panel (OncoScreen ST2.0). In-house sporadic CRCs and The Cancer Genome Atlas project data were used for comparison. Fifty-five IBD-CRCs from 48 patients were successfully analyzed. Mutations in TP53 were most common and were present in 69% of IBD-CRCs; a similar percentage of TP53 mutations was detected in sporadic colorectal carcinomas (70%). APC and KRAS mutations were significantly less common in IBD-CRCs than in sporadic CRCs (15% versus 53%, P <.001 and 20% versus 38%, P =.02, respectively). Additionally, the potentially targetable IDH1 R132 mutation was present in 7% of IBD-CRCs but only 1% of sporadic CRCs and The Cancer Genome Atlas CRCs; alterations in other genes with potential targeted therapies were very rare. In conclusion, IBD-CRCs exhibit molecular differences when compared to sporadic CRCs, suggesting different pathways of carcinogenesis, although certain alterations are common to both types of tumors. IDH1 mutations are present in a subset of IBD-CRCs, which may expand therapeutic options in the future.

Original languageEnglish (US)
Pages (from-to)44-50
Number of pages7
JournalHuman pathology
Volume89
DOIs
StatePublished - Jul 2019

Keywords

  • Colorectal cancer
  • Crohn disease
  • Inflammatory bowel disease
  • Molecular analysis
  • Ulcerative colitis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Alpert, L., Yassan, L., Poon, R., Kadri, S., Niu, N., Patil, S. A., Mujacic, I., Montes, D., Galbo, F., Wurst, M. N., Zhen, C. J., Cohen, R. D., Rubin, D. T., Pekow, J. R., Weber, C. R., Xiao, S. Y., Hart, J., Segal, J., & Setia, N. (2019). Targeted mutational analysis of inflammatory bowel disease–associated colorectal cancers. Human pathology, 89, 44-50. https://doi.org/10.1016/j.humpath.2019.04.013