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Somatic Mosaicism for Cancer Predisposition Genes and Pancreatic Cancer

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Technical Report,15 Jun 2016,14 Jun 2019

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Sloan Kettering Institute for Cancer Research New York United States

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Somatic mosaicism refers to the occurrence of two genetically distinct populations of cells within an individual, derived from a postzygotic mutation. Unlike inherited mutations in which the variant allele is present in all cells in the body, somatic mosaic mutations may affect only a subset of cells and may not be passed on to their progeny. The extent to which somatic mosaicism for PDA cancer predisposition genes accounts for PDA incidence is unknown. We performed targeted sequencing using the MSK-IMPACT platform containing 468 cancer genes to sequence 256 normal tissues from 35 patients, including their matched tumor tissues. We note that somatic mosaicism is indeed present in our patient cohort as evidenced by mutations private to a single normal tissue. These variants are in known driver genes and some are predicted to have deleterious consequences. We have also found recurrent somatic alterations in a subset in genes, most often in the Androgen Receptor. The significance of this findings is unknown but quite provocative, as they are confined to solid tissues only and not the blood in the patients they are found in. The most common variant identified affects G473 as an inframe deletion of various sizes i.e. AR p.G473del, or AR p. G465G473del. Skin and lung contains on average double the number of mutations than other normal tissues, consistent with UV and environmental damage over the lifetime of the patients.

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  • Medicine and Medical Research

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