Germline variants in patients diagnosed with pediatric soft tissue sarcoma

Area of Science:

• Oncology
• Genetics
• Pediatric Medicine

Background:

• Soft tissue sarcomas are diagnosed in younger individuals.
• Limited research exists on the prevalence of germline variants in pediatric and young adult sarcoma patients.

Purpose of the Study:

• To investigate the distribution and spectrum of pathogenic germline variants in young patients diagnosed with soft tissue sarcoma.

Main Methods:

• Retrospective analysis of pediatric and young adult patients (0-22 years) diagnosed between 1981-2019.
• Targeted sequencing of 360 cancer genes in normal tissue samples from 41 patients.
• Analysis of tumor tissue for loss of heterozygosity and additional somatic variants.

Main Results:

• Pathogenic germline variants (PVs) were identified in 7 out of 41 (17%) analyzed cases.
• Identified PVs were in genes including TP53, MUTYH, FANCC, DICER1, FANCA, MYO3A, and MYO5B.
• Evidence supporting causality included loss of heterozygosity, secondary somatic variants, and allele amplification in tumor tissues.

Conclusions:

• A substantial fraction of young soft tissue sarcoma patients harbor PVs.
• The study substantiates a potential role for MYO5B and proposes a potential role for MYO3A in sarcoma pathogenesis.