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Germline PALB2 Mutations in Cancers and Its Distinction From Somatic PALB2 Mutations in Breast Cancers
PALB2 is an important BRCAx candidate for familial breast cancers (FBC). PALB2 pathogenic variants (PVs) may not to conform to “two hit” paradigm. However, a recent study demonstrates that in the majority PALB2 germline mutant breast cancers, the loss of heterozygosity (LOH) and somatic point mutati...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482549/ https://www.ncbi.nlm.nih.gov/pubmed/33193564 http://dx.doi.org/10.3389/fgene.2020.00829 |
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author | Hu, Zhe-Yu Liu, Liping Xie, Ning Lu, Jun Liu, Zhentian Tang, Yu Wang, Yikai Yang, Jianbo Ouyang, Quchang |
author_facet | Hu, Zhe-Yu Liu, Liping Xie, Ning Lu, Jun Liu, Zhentian Tang, Yu Wang, Yikai Yang, Jianbo Ouyang, Quchang |
author_sort | Hu, Zhe-Yu |
collection | PubMed |
description | PALB2 is an important BRCAx candidate for familial breast cancers (FBC). PALB2 pathogenic variants (PVs) may not to conform to “two hit” paradigm. However, a recent study demonstrates that in the majority PALB2 germline mutant breast cancers, the loss of heterozygosity (LOH) and somatic point mutations are the “second hit.” This study aimed to investigate the second hits in germline PALB2 mutations in breast cancers. We screened out 28 germline PALB2-mutation carriers among 480 familial cancer patients (including 143 FBC patients) in Geneplus database pool. Of the 143 patients with FBC, 10 had mono-allelic PALB2 germline mutations. All these germline PALB2 mutations were high-risk stop-gain, frameshift, or splicing mutations that concentrated in EX5–EX9 and might led to truncated proteins, severe functional defects and malignant phenotype. The hotspots were c.1057A[3 > 2] and c.3114-1G > A. Other mutations included c.389delA, c.2068C > T, c.2167_2168delAT, c.2629delT and c.2968G > T. Only one FBC patient has PALB2 somatic mutation and two patients had LOH of PALB2. All germline PALB2 mutations were high-risk mutations, whereas the somatic PALB2 mutations were moderate-risk missense mutations. We also distinguished PALB2 “novel mutations” from “reported mutations.” In conclusion, germline PALB2 mutation should be put into the context of future screening. |
format | Online Article Text |
id | pubmed-7482549 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-74825492020-11-12 Germline PALB2 Mutations in Cancers and Its Distinction From Somatic PALB2 Mutations in Breast Cancers Hu, Zhe-Yu Liu, Liping Xie, Ning Lu, Jun Liu, Zhentian Tang, Yu Wang, Yikai Yang, Jianbo Ouyang, Quchang Front Genet Genetics PALB2 is an important BRCAx candidate for familial breast cancers (FBC). PALB2 pathogenic variants (PVs) may not to conform to “two hit” paradigm. However, a recent study demonstrates that in the majority PALB2 germline mutant breast cancers, the loss of heterozygosity (LOH) and somatic point mutations are the “second hit.” This study aimed to investigate the second hits in germline PALB2 mutations in breast cancers. We screened out 28 germline PALB2-mutation carriers among 480 familial cancer patients (including 143 FBC patients) in Geneplus database pool. Of the 143 patients with FBC, 10 had mono-allelic PALB2 germline mutations. All these germline PALB2 mutations were high-risk stop-gain, frameshift, or splicing mutations that concentrated in EX5–EX9 and might led to truncated proteins, severe functional defects and malignant phenotype. The hotspots were c.1057A[3 > 2] and c.3114-1G > A. Other mutations included c.389delA, c.2068C > T, c.2167_2168delAT, c.2629delT and c.2968G > T. Only one FBC patient has PALB2 somatic mutation and two patients had LOH of PALB2. All germline PALB2 mutations were high-risk mutations, whereas the somatic PALB2 mutations were moderate-risk missense mutations. We also distinguished PALB2 “novel mutations” from “reported mutations.” In conclusion, germline PALB2 mutation should be put into the context of future screening. Frontiers Media S.A. 2020-08-27 /pmc/articles/PMC7482549/ /pubmed/33193564 http://dx.doi.org/10.3389/fgene.2020.00829 Text en Copyright © 2020 Hu, Liu, Xie, Lu, Liu, Tang, Wang, Yang and Ouyang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Hu, Zhe-Yu Liu, Liping Xie, Ning Lu, Jun Liu, Zhentian Tang, Yu Wang, Yikai Yang, Jianbo Ouyang, Quchang Germline PALB2 Mutations in Cancers and Its Distinction From Somatic PALB2 Mutations in Breast Cancers |
title | Germline PALB2 Mutations in Cancers and Its Distinction From Somatic PALB2 Mutations in Breast Cancers |
title_full | Germline PALB2 Mutations in Cancers and Its Distinction From Somatic PALB2 Mutations in Breast Cancers |
title_fullStr | Germline PALB2 Mutations in Cancers and Its Distinction From Somatic PALB2 Mutations in Breast Cancers |
title_full_unstemmed | Germline PALB2 Mutations in Cancers and Its Distinction From Somatic PALB2 Mutations in Breast Cancers |
title_short | Germline PALB2 Mutations in Cancers and Its Distinction From Somatic PALB2 Mutations in Breast Cancers |
title_sort | germline palb2 mutations in cancers and its distinction from somatic palb2 mutations in breast cancers |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482549/ https://www.ncbi.nlm.nih.gov/pubmed/33193564 http://dx.doi.org/10.3389/fgene.2020.00829 |
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