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

Journal of Human Genetics volume 68, pages 399–408 (2023)Cite this article

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Abstract

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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Acknowledgements

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

Author information

Authors and Affiliations

  1. Personalized Medicine Center, Tohoku University Hospital, Sendai, Japan

    Maako Kawamura & Ikuko Sugiyama

  2. Department of Clinical Oncology, Tohoku University Hospital, Sendai, Japan

    Hidekazu Shirota, Keigo Komine, Masanobu Takahashi, Shin Takahashi & Chikashi Ishioka

  3. Department of Medical Genetics, Tohoku University Graduate School of Medicine, Sendai, Japan

    Tetsuya Niihori, Mari Tsubata & Yoko Aoki

  4. Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan

    Eisaku Miyauchi

  5. Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan

    Hidetaka Niizuma & Atsuo Kikuchi

  6. Department of Breast and Endocrine Surgical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan

    Hiroshi Tada

  7. Department of Obstetrics and Gynecology, Tohoku University School of Medicine, Sendai, Japan

    Muneaki Shimada

  8. Department of Urology, Tohoku University School of Medicine, Sendai, Japan

    Naoki Kawamorita

  9. Department of Neurosurgery, Tohoku University School of Medicine, Sendai, Japan

    Masayuki Kanamori

  10. Department of Clinical Genomics, National Cancer Center Research Institute, Tokyo, Japan

    Hitotshi Ichikawa

  11. Division of Molecular Cellular Oncology, Miyagi Cancer Center Research Institute, Natori, Japan

    Jun Yasuda

  12. Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan

    Toru Furukawa

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  1. Maako Kawamura
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  8. Hidetaka Niizuma
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  19. Yoko Aoki
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  20. Chikashi Ishioka
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Corresponding authors

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). https://doi.org/10.1038/s10038-023-01133-5

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