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Management of patients with presumed germline pathogenic variant from tumor-only genomic sequencing: A retrospective analysis at a single facility


Cancer treatment is increasingly evolving toward personalized medicine, which sequences numerous cancer-related genes and identifies therapeutic targets. On the other hand, patients with germline pathogenic variants (GPV) have been identified as secondary findings (SF) and oncologists have been urged to handle them. All SF disclosure considerations for patients are addressed and decided at the molecular tumor boards (MTB) in the facility. In this study, we retrospectively summarized the results of all cases in which comprehensive genomic profiling (CGP) test was conducted at our hospital, and discussed the possibility of presumed germline pathogenic variants (PGPV) at MTB. MTB recommended confirmatory testing for 64 patients. Informed consent was obtained from attending physicians for 53 of them, 30 patients requested testing, and 17 patients tested positive for a confirmatory test. Together with already known variants, 4.5 % of the total confirmed in this cohort. Variants verified in this study were BRCA1 (n = 12), BRCA2 (n = 6), MSH2 (n = 2), MSH6 (n = 2), WT1 (n = 2), TP53, MEN1, CHEK2, MLH1, TSC2, PTEN, RB1, and SMARCB1. There was no difference in the tumor’s VAF between confirmed positive and negative cases for variants determined as PGPV by MTB. Current results demonstrate the actual number of cases until confirmatory germline test for patients with PGPV from tumor-only CGP test through the discussion at the MTB. The practical results at this single facility will serve as a guide for the management of the selection and distribution of SF in the genome analysis.

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The authors would like to thank all the physicians who attended our MTB meeting.

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Correspondence to Hidekazu Shirota or Chikashi Ishioka.

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Competing interests

Dr. Ishioka has received scholarship (incentive) endowments from Takeda, Daiichi-Sankyo, Ono, Asahi-Kasei Pharma, Taiho, and Chugai, as well as a research grant from Hitachi and Riken Genesis. Dr. Ichikawa has received research grants from Chugai Pharmaceutical, Eisai, Healios, and Ono Pharmaceutical, outside the submitted work. All remaining authors have declared no conflict of interest.

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Kawamura, M., Shirota, H., Niihori, T. et al. Management of patients with presumed germline pathogenic variant from tumor-only genomic sequencing: A retrospective analysis at a single facility. J Hum Genet 68, 399–408 (2023).

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