The Concordance of Secondary Pathogenic Germline Variants Identified by Tumor Genomic Profiling in Adult Solid Tumor...

Secondary pathogenic/likely pathogenic germline variants (P/LPGVs) identified on solid tumor genomic profiling (TGP) are a commonly encountered clinical issue. A proportion of oncology patients that undergo TGP will have a secondary P/LPGV identified that may not have been otherwise discovered based on clinical and family history criteria for hereditary cancer syndrome screening. The confirmation of P/LPGVs on germline sequencing has potential treatment implications for patients.

The study design was a retrospective review for secondary data analysis. The inclusion criteria for this study were adult patients with solid tumor malignancy who underwent TGP and germline sequencing. The objective of this study is to evaluate the concordance rate of secondary P/LPGVs on TGP of adult patients with solid tumor malignancy at Hoag Presbyterian Hospital and Tower Health-Reading Hospital. The second and third aims are to analyze if the confirmed P/LPGVs are concordant with the patient's tumor type and to analyze the variant allele frequencies (VAFs) of the identified secondary P/LPGVs on the tumor genomic profiling.

The data included 75 patients who underwent both TGP and germline sequencing, with a median age of 62.5 years. The most represented genes with P/LPGVs in the combined data included BRCA1 and BRCA2, both with 14, and MSH2, with 9. The overall germline concordance rate for the combined population was 64.1%, with 59 out of 92 P/LPGVs identified on both germline and somatic tumor testing.

The overall germline concordance rate of 64% for the combined population is in accordance with the reported literature. Possible reasons for the variability in rates could be related to reporting guidelines for secondary germline variants, which can vary by company, and differences between somatic and germline variant curation. The study of P/LPGVs in populations from community cancer centers has the potential to increase the data of underrepresented minority groups regarding this important clinical issue and help expand understanding of hereditary cancer syndrome phenotypes.