Comprehensive germline genomic profiles of children, adolescents and young adults with solid tumors

Sara Akhavanfard, Roshan Padmanabhan, Lamis Yehia, Feixiong Cheng and Charis Eng ()
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Sara Akhavanfard: Cleveland Clinic
Roshan Padmanabhan: Cleveland Clinic
Lamis Yehia: Cleveland Clinic
Feixiong Cheng: Cleveland Clinic
Charis Eng: Cleveland Clinic

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract Compared to adult carcinomas, there is a paucity of targeted treatments for solid tumors in children, adolescents, and young adults (C-AYA). The impact of germline genomic signatures has implications for heritability, but its impact on targeted therapies has not been fully appreciated. Performing variant-prioritization analysis on germline DNA of 1,507 C-AYA patients with solid tumors, we show 12% of these patients carrying germline pathogenic and/or likely pathogenic variants (P/LP) in known cancer-predisposing genes (KCPG). An additional 61% have germline pathogenic variants in non-KCPG genes, including PRKN, SMARCAL1, SMAD7, which we refer to as candidate genes. Despite germline variants in a broad gene spectrum, pathway analysis leads to top networks centering around p53. Our drug-target analysis shows 1/3 of patients with germline P/LP variants have at least one druggable alteration, while more than half of them are from our candidate gene group, which would otherwise go unidentified in routine clinical care.

Date: 2020
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DOI: 10.1038/s41467-020-16067-1

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