GERMLINE PREDISPOSITION: A study of 1,507 children, adolescents and young adults with cancer found pathogenic/likely pathogenic germline cancer predisposition alleles in 12%

Kevin Sovet

May 18, 2020

SCIENTIFIC

GERMLINE PREDISPOSITION

A study of 1,507 children, adolescents and young adults with cancer found pathogenic/likely pathogenic germline cancer predisposition alleles in 12%

 

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

Nature Communications volume 11, Article number: 2206 (2020) 

 

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 PRKNSMARCAL1SMAD7, 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.

 

more info : https://www.nature.com/articles/s41467-020-16067-1