Abstract 1780P
Background
European Society for Medical Oncology Precision Medicine Working Group (ESMO-PMWG) published the recommendations regarding germline follow-up testing of tumour-only sequencing based on tumour-normal sequencing data (Mandelker D. Ann Oncol 2019). Clinical studies examining whether this criterion can be applied in daily clinical practice are limited.
Methods
Medical records of 151 consecutive patients who underwent a tumour-only comprehensive genomic profiling assay (FoundationOne® companion diagnostic, F1CDx) between October 2018 and June 2019 were reviewed. Among them, 109 patients who provided their peripheral blood samples for research purpose were considered eligible. We then manually selected the tumour detected pathogenic variants of potential germline origin (TDPVs) from the F1CDx report and performed germline follow-up testing using the DNA from blood samples archived in our cancer biobanking. Pathogenicity of the confirmed germline variants was interpreted based on the American College of Medical Genetics and Genomics/Association for Molecular Pathology 2015 guideline.
Results
Median age was 65.5 years (range, 24-84 years), 58 patients were male (53.2%), 94 patients had gastrointestinal cancers and 15 had rare malignancies or cancers of unknown primary site. Furthermore, 109 TDPVs reported in the F1CDx matched the ESMO-PMWG actionable cancer susceptibility genes. According to ESMO-PMWG recommendations, BRCA2 (n = 3), BRIP1 (n = 1), BAP1 (n = 1), and SDHB (n = 1) met the recommendation for germline follow-up testing. Germline sequencing confirmed that BRCA2 (n = 2), BRIP1 (n = 1), and SDHB (n = 1) were of germline origin (67.7%). Thus, the threshold of ESMO-PMWG recommendation for germline follow-up testing was achieved. Nevertheless, among the 103 TDPVs, which did not meet the ESMO-PMWG recommendation for germline follow-up testing, MEN1 (n = 1) and NF1 (n = 1) were confirmed to be of germline origin (1.98 %).
Conclusions
In total, 6 out of the 109 patients (5.5%) were confirmed to harbor pathogenic variants of germline origin. ESMO-PMWG recommendation criteria are helpful in daily clinical practice to identify pathogenic germline variants in tumour-only sequencing.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Chugai Pharmaceutical Co., Ltd.
Disclosure
M. Muto: Financial Interests, Personal and Institutional, Funding: Chugai Pharmaceutical Co., Ltd.. All other authors have declared no conflicts of interest.