Genetic Testing Utilization: Discrepancies Between Somatic and Germline Results in Patients With Cancer Reviewed at the UW Health Precision Medicine Molecular Tumor Board

Abstract

PURPOSE Somatic and germline testing are increasingly used to estimate risks for patients with cancer. Although both germline testing and somatic testing can identify genetic variants that could change a patient's care and eligible treatments, the aims of these tests and their technologies are fundamentally different and cannot be used interchangeably. This study examines the timing and results of somatic and germline genetic testing for patients with cancer at UW Health. METHODS Eight hundred and seventy-seven participants underwent somatic genetic testing, which was reviewed by the Precision Medicine Molecular Tumor Board (PMMTB). Patients were diagnosed with cancers, including breast, colorectal, endometrial, pancreatic, or ovarian cancer, and met National Comprehensive Cancer Network criteria for germline genetic testing. Germline testing details were collected by medical record review. RESULTS The results of this study found that only 310 patients (35%) had germline evaluation before PMMTB review. The percent of germline pathogenic/likely pathogenic variants identified in actionable genes was 28%. Most germline variants were identified in the BRCA1 (26%) and BRCA2 (28%) genes. In total, 65% (54/83) of germline variants were detected with both germline testing and somatic testing; however, 35% (29/83) of germline variants were not identified on somatic results. These results demonstrate the importance of combination germline and somatic testing. CONCLUSION This study highlights the differences in genetic testing types and demonstrates that conducting germline testing at earlier stages of diagnoses is necessary to identify potentially actionable and treatment-specific variants in patients with cancer.

Tumor-Only Sequencing: A Story Only Half Told

“…In the article that accompanies this editorial, Horn et al 15 present the experience of an academic health care center, the UW Health Precision Medicine Molecular Tumor Board, regarding the discrepancies between germline and somatic variants identified in their patients with advanced cancer. They found that only 50% of their patients who were eligible for germline analysis based on current guidelines received germline testing following tumor sequencing in their institution.…”

“…The study by Horn et al 15 also highlights how critical the timing of germline analysis can be for the clinical management of patients with advanced cancer. Many patients in their study cohort only received germline testing after developing advanced disease and following tumor sequencing, although they were eligible for germline evaluation based on their cancer type and age at onset at the time of diagnosis.…”