Editors' ChoiceUlcerative Colitis

Catching Cancer Early

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Science Translational Medicine  25 Nov 2009:
Vol. 1, Issue 8, pp. 8ec30
DOI: 10.1126/scitranslmed.3000639

Ulcerative colitis is an inflammatory bowel disease that can cast a large shadow over patients' quality of life, as it can cause periods of constant, bloody diarrhea, and severe abdominal cramps. Even worse, it also predisposes to colon cancer, which eventually develops in as many as 10% of these patients. Because the early signs of ulcerative colitis–associated cancer are difficult to see with an endoscope, biopsies at many random sites in the colon are usually taken every year or two, a costly procedure that can only detect morphological changes. An alternative surveillance plan might be to screen the colon for genetic alterations that signal cancer progression, potentially allowing earlier detection. Recent work suggests, however, that the genetic alterations that drive cancer progression can be quite diverse, so some uncommon changes would not be detected in a screen for standard markers. Now, Salk et al. test a different idea—that the presence of expanded clones of cells in the colon indicates progression toward cancer in ulcerative colitis—based on the concept that individual progenitor cells undergo mutation, selection, and clonal expansion as cancers develop. This approach could get around the problem that many cancer-associated mutations are functionally silent. The researchers found that neutral mutations in polyguanine tracts—repetitive sequences that undergo frequent insertions and deletions—could be detected in patches of clonally expanded cells in the diseased colon. Furthermore, they found that such clones only appeared in morphologically normal regions of the colon in patients with recognizable disease elsewhere in the colon, but not in those without. These results indicate that a test for islands of expanded cells could be clinically useful, perhaps identifying patients at risk for developing cancer.

J. J. Salk et al., Clonal expansions in ulcerative colitis identify patients with neoplasia. Proc. Natl. Acad. Sci. U.S.A. 19 November 2009 (10.1073/pnas.0909428106) [Full Text]

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