Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Kaneyasu, Tomoko, Mori, Seiichi, Yamauchi, Hideko, Ohsumi, Shozo, Ohno, Shinji, Aoki, Daisuke, Baba, Shinichi, Kawano, Junko, Miki, Yoshio, Matsumoto, Naomichi, Nagasaki, Masao, Yoshida, Reiko, Akashi-Tanaka, Sadako, Iwase, Takuji, Kitagawa, Dai, Masuda, Kenta, Hirasawa, Akira, Arai, Masami, Takei, Junko, Ide, Yoshimi, Gotoh, Osamu, Yaguchi, Noriko, Nishi, Mitsuyo, Kaneko, Keika, Matsuyama, Yumi, Okawa, Megumi, Suzuki, Misato, Nezu, Aya, Yokoyama, Shiro, Amino, Sayuri, Inuzuka, Mayuko, Noda, Tetsuo, Nakamura, Seigo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293299/
https://www.ncbi.nlm.nih.gov/pubmed/32566746
http://dx.doi.org/10.1038/s41523-020-0163-1
_version_ 1783546273509408768
author Kaneyasu, Tomoko
Mori, Seiichi
Yamauchi, Hideko
Ohsumi, Shozo
Ohno, Shinji
Aoki, Daisuke
Baba, Shinichi
Kawano, Junko
Miki, Yoshio
Matsumoto, Naomichi
Nagasaki, Masao
Yoshida, Reiko
Akashi-Tanaka, Sadako
Iwase, Takuji
Kitagawa, Dai
Masuda, Kenta
Hirasawa, Akira
Arai, Masami
Takei, Junko
Ide, Yoshimi
Gotoh, Osamu
Yaguchi, Noriko
Nishi, Mitsuyo
Kaneko, Keika
Matsuyama, Yumi
Okawa, Megumi
Suzuki, Misato
Nezu, Aya
Yokoyama, Shiro
Amino, Sayuri
Inuzuka, Mayuko
Noda, Tetsuo
Nakamura, Seigo
author_facet Kaneyasu, Tomoko
Mori, Seiichi
Yamauchi, Hideko
Ohsumi, Shozo
Ohno, Shinji
Aoki, Daisuke
Baba, Shinichi
Kawano, Junko
Miki, Yoshio
Matsumoto, Naomichi
Nagasaki, Masao
Yoshida, Reiko
Akashi-Tanaka, Sadako
Iwase, Takuji
Kitagawa, Dai
Masuda, Kenta
Hirasawa, Akira
Arai, Masami
Takei, Junko
Ide, Yoshimi
Gotoh, Osamu
Yaguchi, Noriko
Nishi, Mitsuyo
Kaneko, Keika
Matsuyama, Yumi
Okawa, Megumi
Suzuki, Misato
Nezu, Aya
Yokoyama, Shiro
Amino, Sayuri
Inuzuka, Mayuko
Noda, Tetsuo
Nakamura, Seigo
author_sort Kaneyasu, Tomoko
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7293299
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-72932992020-06-19 Prevalence of disease-causing genes in Japanese patients with BRCA1/2-wildtype hereditary breast and ovarian cancer syndrome Kaneyasu, Tomoko Mori, Seiichi Yamauchi, Hideko Ohsumi, Shozo Ohno, Shinji Aoki, Daisuke Baba, Shinichi Kawano, Junko Miki, Yoshio Matsumoto, Naomichi Nagasaki, Masao Yoshida, Reiko Akashi-Tanaka, Sadako Iwase, Takuji Kitagawa, Dai Masuda, Kenta Hirasawa, Akira Arai, Masami Takei, Junko Ide, Yoshimi Gotoh, Osamu Yaguchi, Noriko Nishi, Mitsuyo Kaneko, Keika Matsuyama, Yumi Okawa, Megumi Suzuki, Misato Nezu, Aya Yokoyama, Shiro Amino, Sayuri Inuzuka, Mayuko Noda, Tetsuo Nakamura, Seigo NPJ Breast Cancer Article 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. Nature Publishing Group UK 2020-06-12 /pmc/articles/PMC7293299/ /pubmed/32566746 http://dx.doi.org/10.1038/s41523-020-0163-1 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Kaneyasu, Tomoko
Mori, Seiichi
Yamauchi, Hideko
Ohsumi, Shozo
Ohno, Shinji
Aoki, Daisuke
Baba, Shinichi
Kawano, Junko
Miki, Yoshio
Matsumoto, Naomichi
Nagasaki, Masao
Yoshida, Reiko
Akashi-Tanaka, Sadako
Iwase, Takuji
Kitagawa, Dai
Masuda, Kenta
Hirasawa, Akira
Arai, Masami
Takei, Junko
Ide, Yoshimi
Gotoh, Osamu
Yaguchi, Noriko
Nishi, Mitsuyo
Kaneko, Keika
Matsuyama, Yumi
Okawa, Megumi
Suzuki, Misato
Nezu, Aya
Yokoyama, Shiro
Amino, Sayuri
Inuzuka, Mayuko
Noda, Tetsuo
Nakamura, Seigo
Prevalence of disease-causing genes in Japanese patients with BRCA1/2-wildtype hereditary breast and ovarian cancer syndrome
title Prevalence of disease-causing genes in Japanese patients with BRCA1/2-wildtype hereditary breast and ovarian cancer syndrome
title_full Prevalence of disease-causing genes in Japanese patients with BRCA1/2-wildtype hereditary breast and ovarian cancer syndrome
title_fullStr Prevalence of disease-causing genes in Japanese patients with BRCA1/2-wildtype hereditary breast and ovarian cancer syndrome
title_full_unstemmed Prevalence of disease-causing genes in Japanese patients with BRCA1/2-wildtype hereditary breast and ovarian cancer syndrome
title_short Prevalence of disease-causing genes in Japanese patients with BRCA1/2-wildtype hereditary breast and ovarian cancer syndrome
title_sort prevalence of disease-causing genes in japanese patients with brca1/2-wildtype hereditary breast and ovarian cancer syndrome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293299/
https://www.ncbi.nlm.nih.gov/pubmed/32566746
http://dx.doi.org/10.1038/s41523-020-0163-1
work_keys_str_mv AT kaneyasutomoko prevalenceofdiseasecausinggenesinjapanesepatientswithbrca12wildtypehereditarybreastandovariancancersyndrome
AT moriseiichi prevalenceofdiseasecausinggenesinjapanesepatientswithbrca12wildtypehereditarybreastandovariancancersyndrome
AT yamauchihideko prevalenceofdiseasecausinggenesinjapanesepatientswithbrca12wildtypehereditarybreastandovariancancersyndrome
AT ohsumishozo prevalenceofdiseasecausinggenesinjapanesepatientswithbrca12wildtypehereditarybreastandovariancancersyndrome
AT ohnoshinji prevalenceofdiseasecausinggenesinjapanesepatientswithbrca12wildtypehereditarybreastandovariancancersyndrome
AT aokidaisuke prevalenceofdiseasecausinggenesinjapanesepatientswithbrca12wildtypehereditarybreastandovariancancersyndrome
AT babashinichi prevalenceofdiseasecausinggenesinjapanesepatientswithbrca12wildtypehereditarybreastandovariancancersyndrome
AT kawanojunko prevalenceofdiseasecausinggenesinjapanesepatientswithbrca12wildtypehereditarybreastandovariancancersyndrome
AT mikiyoshio prevalenceofdiseasecausinggenesinjapanesepatientswithbrca12wildtypehereditarybreastandovariancancersyndrome
AT matsumotonaomichi prevalenceofdiseasecausinggenesinjapanesepatientswithbrca12wildtypehereditarybreastandovariancancersyndrome
AT nagasakimasao prevalenceofdiseasecausinggenesinjapanesepatientswithbrca12wildtypehereditarybreastandovariancancersyndrome
AT yoshidareiko prevalenceofdiseasecausinggenesinjapanesepatientswithbrca12wildtypehereditarybreastandovariancancersyndrome
AT akashitanakasadako prevalenceofdiseasecausinggenesinjapanesepatientswithbrca12wildtypehereditarybreastandovariancancersyndrome
AT iwasetakuji prevalenceofdiseasecausinggenesinjapanesepatientswithbrca12wildtypehereditarybreastandovariancancersyndrome
AT kitagawadai prevalenceofdiseasecausinggenesinjapanesepatientswithbrca12wildtypehereditarybreastandovariancancersyndrome
AT masudakenta prevalenceofdiseasecausinggenesinjapanesepatientswithbrca12wildtypehereditarybreastandovariancancersyndrome
AT hirasawaakira prevalenceofdiseasecausinggenesinjapanesepatientswithbrca12wildtypehereditarybreastandovariancancersyndrome
AT araimasami prevalenceofdiseasecausinggenesinjapanesepatientswithbrca12wildtypehereditarybreastandovariancancersyndrome
AT takeijunko prevalenceofdiseasecausinggenesinjapanesepatientswithbrca12wildtypehereditarybreastandovariancancersyndrome
AT ideyoshimi prevalenceofdiseasecausinggenesinjapanesepatientswithbrca12wildtypehereditarybreastandovariancancersyndrome
AT gotohosamu prevalenceofdiseasecausinggenesinjapanesepatientswithbrca12wildtypehereditarybreastandovariancancersyndrome
AT yaguchinoriko prevalenceofdiseasecausinggenesinjapanesepatientswithbrca12wildtypehereditarybreastandovariancancersyndrome
AT nishimitsuyo prevalenceofdiseasecausinggenesinjapanesepatientswithbrca12wildtypehereditarybreastandovariancancersyndrome
AT kanekokeika prevalenceofdiseasecausinggenesinjapanesepatientswithbrca12wildtypehereditarybreastandovariancancersyndrome
AT matsuyamayumi prevalenceofdiseasecausinggenesinjapanesepatientswithbrca12wildtypehereditarybreastandovariancancersyndrome
AT okawamegumi prevalenceofdiseasecausinggenesinjapanesepatientswithbrca12wildtypehereditarybreastandovariancancersyndrome
AT suzukimisato prevalenceofdiseasecausinggenesinjapanesepatientswithbrca12wildtypehereditarybreastandovariancancersyndrome
AT nezuaya prevalenceofdiseasecausinggenesinjapanesepatientswithbrca12wildtypehereditarybreastandovariancancersyndrome
AT yokoyamashiro prevalenceofdiseasecausinggenesinjapanesepatientswithbrca12wildtypehereditarybreastandovariancancersyndrome
AT aminosayuri prevalenceofdiseasecausinggenesinjapanesepatientswithbrca12wildtypehereditarybreastandovariancancersyndrome
AT inuzukamayuko prevalenceofdiseasecausinggenesinjapanesepatientswithbrca12wildtypehereditarybreastandovariancancersyndrome
AT nodatetsuo prevalenceofdiseasecausinggenesinjapanesepatientswithbrca12wildtypehereditarybreastandovariancancersyndrome
AT nakamuraseigo prevalenceofdiseasecausinggenesinjapanesepatientswithbrca12wildtypehereditarybreastandovariancancersyndrome