Prevalence of disease-causing genes in Japanese patients with BRCA1/2-wildtype hereditary breast and ovarian cancer syndrome View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2020-06-12

AUTHORS

Tomoko Kaneyasu, Seiichi Mori, Hideko Yamauchi, Shozo Ohsumi, Shinji Ohno, Daisuke Aoki, Shinichi Baba, Junko Kawano, Yoshio Miki, Naomichi Matsumoto, Masao Nagasaki, Reiko Yoshida, Sadako Akashi-Tanaka, Takuji Iwase, Dai Kitagawa, Kenta Masuda, Akira Hirasawa, Masami Arai, Junko Takei, Yoshimi Ide, Osamu Gotoh, Noriko Yaguchi, Mitsuyo Nishi, Keika Kaneko, Yumi Matsuyama, Megumi Okawa, Misato Suzuki, Aya Nezu, Shiro Yokoyama, Sayuri Amino, Mayuko Inuzuka, Tetsuo Noda, Seigo Nakamura

ABSTRACT

Panel sequencing of susceptibility genes for hereditary breast and ovarian cancer (HBOC) syndrome has uncovered numerous germline variants; however, their pathogenic relevance and ethnic diversity remain unclear. Here, we examined the prevalence of germline variants among 568 Japanese patients with BRCA1/2-wildtype HBOC syndrome and a strong family history. Pathogenic or likely pathogenic variants were identified on 12 causal genes for 37 cases (6.5%), with recurrence for 4 SNVs/indels and 1 CNV. Comparisons with non-cancer east-Asian populations and European familial breast cancer cohorts revealed significant enrichment of PALB2, BARD1, and BLM mutations. Younger onset was associated with but not predictive of these mutations. Significant somatic loss-of-function alterations were confirmed on the wildtype alleles of genes with germline mutations, including PALB2 additional somatic truncations. This study highlights Japanese-associated germline mutations among patients with BRCA1/2 wildtype HBOC syndrome and a strong family history, and provides evidence for the medical care of this high-risk population. More... »

PAGES

25

References to SciGraph publications

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  • Journal

    TITLE

    npj Breast Cancer

    ISSUE

    1

    VOLUME

    6

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41523-020-0163-1

    DOI

    http://dx.doi.org/10.1038/s41523-020-0163-1

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1128422390

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/32566746


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