Evolutionary genetic tools trace cancer clone lines

Sophisticated computational tools developed to trace species evolution by comparing DNA sequences have now been used to track the development of human cancer.

The collaboration by a USC team led by cancer researcher Darryl Shibata and computational biologist Simon Tavare casts doubt on conventional wisdom regarding the relationship between colorectal cancers (carcinomas) and the polyps (adenomas) which typically precede them.

The preliminary findings, if they can be confirmed, may have clinical significance in considering non-surgical options for treating polyps.

According to Shibata, an associate professor in the USC medical school department of pathology, oncologists have long believed that the development of colon cancer is a progressive and linear process, with a normal cell mutating into adenoma, and the adenoma subsequently mutating further into carcinoma. In this conventional model, the adenoma is the direct precursor or ancestor to the carcinoma.

But according to the new study, published in the June issue of the American Journal of Pathology, genetic evolution analysis indicates that adenoma and carcinoma lines can arise from a common precursor but subsequently develop in parallel. In this scenario, the adenoma is not the "mother" of the carcinoma but rather a cousin.

The finding suggests that the direct progenitor of cancer cells may not be the most prevalent cell in a polyp. The clone comprising the majority of cells in the adenoma is genetically a dead end with respect to the cancer. One important consequence is that in some cases cancer may arise without being preceded by polyps at all, that is, "the true progenitor may be occult," according to Shibata.

The researcher notes that precisely this scenario is sometimes seen when a patient with no symptoms or polyps at one examination is found a year later to have developed colon cancer. Traditionally, it had been thought that the initial examination simply missed fi

Contact: Eric Mankin
University of Southern California

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