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Analysis of PALB2 mutations in 155 Japanese patients with breast and/or ovarian cancer

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Abstract

Background

PALB2 (Partner and Localizer of BRCA2) was identified as a moderate-risk gene in breast and pancreatic cancers. Recently, it was reported that PALB2 carriers have a high risk of developing breast cancer, with the cumulative risk of 34 % by the age of 70.

Patients and methods

Peripheral blood samples from 155 patients at risk for hereditary breast and/or ovarian cancer were tested for BRCA1/2 and PALB2 by targeted sequencing using a next-generation sequencer. Of these 155, 146 met NCCN criteria and the remaining 9 did not.

Results

BRCA1/2 analysis was performed on 155 patients, for whom the results were reported previously (Hirotsu Y et al. Mol Genet Genomic Med, doi:10.1002/mgg3.157, 2015). Eleven patients were identified to have deleterious BRCA mutations (Hirotsu Y et al. Mol Genet Genomic Med, doi:10.1002/mgg3.157, 2015). However, none of the 155 patients were found to have deleterious PALB2 germline mutations. Missense mutations [variants of uncertain significance (VUS)] of PALB2 were found in 12 cases. In silico analyses by SIFT (Sorting Intolerant Form Tolerant) and PolyPhen2 (Polymorphism Phenotyping version 2) indicated that 2 of 12 VUS were deleterious and probably damaging.

Conclusions

This is the first report on PALB2 mutations in Japan, revealing two missense mutations as “deleterious and probably damaging” by in silico analyses, but no PALB2 premature truncation mutations were identified. The sample size is relatively small and a larger cohort study is needed in Japan.

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Acknowledgments

We thank Takeo Kubota and Satoko Nakagomi for their advice, and Takuro Uchida, Yumi Kubota and Shino Kirito for their assistance. This study was funded by Grant-in-Aid for Genome Research Project from Yamanashi Prefecture.

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Authors and Affiliations

  1. Department of Breast Surgery, Yamanashi Prefectural Central Hospital, 1-1-1 Fujimi, Kofu, 400-0027, Japan

    Hiroshi Nakagomi

  2. Department of Gynecology, Yamanashi Prefectural Central Hospital, 1-1-1 Fujimi, Kofu, 400-0027, Japan

    Ikuko Sakamoto

  3. Genome Analysis Center, Yamanashi Prefectural Central Hospital, 1-1-1 Fujimi, Kofu, 400-0027, Japan

    Yosuke Hirotsu, Kenji Amemiya, Hitoshi Mochiduki & Masao Omata

  4. University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, 113-8654, Japan

    Masao Omata

  5. Department of Surgery, Yamanashi Prefectural Central Hospital, 1-1-1 Fujimi, Kofu, 400-0027, Japan

    Hiroshi Nakagomi

Authors
  1. Hiroshi Nakagomi
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  2. Ikuko Sakamoto
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  3. Yosuke Hirotsu
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  4. Kenji Amemiya
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  5. Hitoshi Mochiduki
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  6. Masao Omata
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Corresponding author

Correspondence to Hiroshi Nakagomi.

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The authors declare no conflict of interest.

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Nakagomi, H., Sakamoto, I., Hirotsu, Y. et al. Analysis of PALB2 mutations in 155 Japanese patients with breast and/or ovarian cancer. Int J Clin Oncol 21, 270–275 (2016). https://doi.org/10.1007/s10147-015-0906-4

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  • DOI: https://doi.org/10.1007/s10147-015-0906-4

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