The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Whole-Exome Sequencing Analyses of Inflammatory Bowel Disease−Associated Colorectal Cancers
Open accessAbstract
BACKGROUND & AIMS A long duration of inflammatory bowel disease (IBD) increases the risk for colorectal cancer (CRC). Mutation analysis of limited numbers of genes has indicated that colorectal tumors that develop in patients with IBD differ from those of patients without IBD. We performed whole-exome sequencing analyses to characterize the genetic landscape of these tumors. METHODS We collected colorectal tumor and non-neoplastic tissues from 31 patients with IBD and CRC (15 with ulcerative colitis, 14 with Crohn’s disease, and 2 with indeterminate colitis) and performed whole-exome sequencing analyses of the micro-dissected tumor and matched non-tumor tissues. We identified somatic alterations by comparing matched specimens. The prevalence of mutations in sporadic colorectal tumors was obtained from previously published exome-sequencing studies. RESULTS Two specimens had somatic mutations in the DNA-proofreading or mismatch repair genes POLE, MLH1, and MSH6 and the tumor cells had a hypermutable phenotype. The remaining tumors had, on average, 71 alterations per sample. TP53 was the most commonly mutated gene, with and incidence prevalence similar to that of sporadic colorectal tumors (63% of cases). However, tumors from the patients with IBD had a different mutation spectrum. APC and KRAS were mutated at significantly lower rates in tumors from patients with IBD than in sporadic colorectal tumors (13% and 20% of cases, respectively). Several genes were mutated more frequently or uniquely in tumors from patients with IBD, including SOX9 and EP300 (which encode proteins in the WNT pathway), NRG1 (which encodes an ERBB ligand), and IL16 (which encodes a cytokine). Our study also revealed recurrent mutations in components of the Rho and Rac GTPase network, indicating a role for non-canonical WNT signaling in development of colorectal tumors in patients with IBD. CONCLUSIONS Colorectal tumors that develop in patients with IBD have distinct genetic features from sporadic colorectal tumors. These findings could be used to develop disease-specific markers for diagnosis and treatment of patients with IBD and CRC.
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Next-Generation Stool DNA Test Accurately Detects Colorectal Cancer and Large Adenomas
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Self-citationSomatic inflammatory gene mutations in human ulcerative colitis epithelium
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Metadata
- Authors
- Robles, A. I., Traverso, G., Zhang, M., Roberts, N. J., Khan, M. A., Joseph, C., Lauwers, G. Y., Selaru, F. M., Popoli, M., Pittman, M. E., Ke, X., Hruban, R. H., Meltzer, S. J., Kinzler, K. W., Vogelstein, B., Harris, C. C., & Papadopoulos, N.
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 150
- Issue
- 4
- Pages
- 931-943
- ISSN
- 0016-5085 (ISSN-L)
- OpenAlex
- W2200646757
- Cited by
- 276
- References
- 9
- FWCI
- 27.10
- Type
- journal article
- Language
- en
- Open access
- green
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- Robles, A. I., Traverso, G., Zhang, M., Roberts, N. J., Khan, M. A., Joseph, C., Lauwers, G. Y., Selaru, F. M., Popoli, M., Pittman, M. E., Ke, X., Hruban, R. H., Meltzer, S. J., Kinzler, K. W., Vogelstein, B., Harris, C. C., & Papadopoulos, N. (2016). Whole-Exome Sequencing Analyses of Inflammatory Bowel Disease−Associated Colorectal Cancers. Gastroenterology. https://doi.org/10.1053/j.gastro.2015.12.036
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