Mosaicism in Patients With Colorectal Cancer or Polyposis Syndromes: a Systematic Review.

Somatic mosaicism arises from genetic alterations that occur after the first division of the zygote, so that not in all cells in the body contain the same genetic variants. These variants might contribute to colorectal cancer (CRC) and polyposis syndromes. We performed a systematic review to provide a comprehensive overview of somatic mosaicism in patients with CRC and polyposis syndromes.We searched PubMed through March 2019 to identify reports of mosaicism in patients with CRC or polyposis syndromes. We divided the final set of studies into 3 subgroups describing APC mosaicism, mosaicism in other genes associated with susceptibility to CRC susceptibility, and epigenetic mosaicism.Of the 232 articles identified in our systematic search, 46 met the criteria for further analysis. Of these, 35 studies described mosaic variants or epimutations in patients with CRC or polyposis syndromes. Nineteen studies described APC mosaicism, comprising a total of 57 patients. Six described mosaicism in genes associated with familial CRC syndromes, such as Lynch and Cowden syndromes. Ten studies described epigenetic mosaicism, sometimes resulting from a germline variant (such as deletion of EPCAM).In a systematic review, we found that many patients with polyposis syndromes have genetic mosaicism, most frequently in APC variants; this information can be used in management of patients. Mosaicism in genes associated with susceptibility to CRC contributes to development of other familial CRC syndromes. Heritable epigenetic mosaicism is likely underestimated and could have a dominant pattern of inheritance. However, the inheritance of primary mosaic epimutations, without an genetic cause, is complex and not fully understood.

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