Pathogenic Germline Variants in Cancer Susceptibility Genes in Children and Young Adults With Rhabdomyosarcoma

Kim J, Light N, Subasri V, Young EL, Wegman-Ostrosky T, Barkauskas DA, Hall D, Lupo PJ, Patidar R, Maese LD, Jones K, Wang M, Tavtigian SV, Wu D, Shlien A, Telfer F, Goldenberg A, Skapek SX, Wei JS, Wen X, Catchpoole D, Hawkins DS, Schiffman JD, Khan J, Malkin D, Stewart DR. Pathogenic Germline Variants in Cancer Susceptibility Genes in Children and Young Adults With Rhabdomyosarcoma. JCO Precis Oncol. 2021;5. doi: 10.1200/PO.20.00218. eCollection 2021. PubMed PMID: 34095712; PubMed Central PMCID: PMC8169077.

Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue sarcoma and accounts for 3% of all pediatric cancer. In this study, we investigated germline sequence and structural variation in a broad set of genes in two large, independent RMS cohorts. Genome sequencing of the discovery cohort (n = 273) and exome sequencing of the secondary cohort (n = 121) were conducted on germline DNA. Analyses were performed on 130 cancer susceptibility genes (CSG). Pathogenic or likely pathogenic (P/LP) variants were predicted using the American College of Medical Genetics and Genomics (ACMG) criteria. Structural variation and survival analyses were performed on the discovery cohort.