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Function: GetPubMedArticleOutput_2016
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Wilms' tumor (WT), the most common childhood kidney cancer, develops in association with an underlying germline predisposition in up to 15% of cases. Germline alterations affecting the WT1 gene and epigenetic alterations affecting the 11p15 locus are associated with a selective increase in WT risk. Nevertheless, WT also occurs in the context of more pleiotropic cancer predispositions, such as DICER1, Li-Fraumeni and Bloom syndrome, as well as Fanconi anemia. Recent germline genomic investigations have increased our understanding of the host genetic factors that influence WT risk, with sequencing of rare familial cases and large WT cohorts revealing an expanding array of predisposition genes and associated genetic conditions. Here, we describe evidence implicating WT1, the 11p15 locus, and the recently identified genes CTR9, REST and TRIM28 in WT predisposition. We discuss the clinical features, mode of inheritance and biological aspects of tumorigenesis, when known. Despite these described associations, many cases of familial WT remain unexplained. Continued investigations are needed to fully elucidate the landscape of germline genetic alterations in children with WT. Establishing a genetic diagnosis is imperative for WT families so that individuals harboring a predisposing germline variant can undergo surveillance, which should enable the early detection of tumors and use of less intensive treatments, thereby leading to improved overall outcomes.
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Source |
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http://dx.doi.org/10.1093/hmg/ddaa091 | DOI Listing |
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