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Assessment of PALB2 as a Candidate Melanoma Susceptibility Gene
Partner and localizer of BRCA2 (PALB2) interacts with BRCA2 to enable double strand break repair through homologous recombination. Similar to BRCA2, germline mutations in PALB2 have been shown to predispose to Fanconi anaemia as well as pancreatic and breast cancer. The PALB2/BRCA2 protein interacti...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4065098/ https://www.ncbi.nlm.nih.gov/pubmed/24949998 http://dx.doi.org/10.1371/journal.pone.0100683 |
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author | Aoude, Lauren G. Xu, Mai Zhao, Zhen Zhen Kovacs, Michael Palmer, Jane M. Johansson, Peter Symmons, Judith Trent, Jeffrey M. Martin, Nicholas G. Montgomery, Grant W. Brown, Kevin M. Hayward, Nicholas K. |
author_facet | Aoude, Lauren G. Xu, Mai Zhao, Zhen Zhen Kovacs, Michael Palmer, Jane M. Johansson, Peter Symmons, Judith Trent, Jeffrey M. Martin, Nicholas G. Montgomery, Grant W. Brown, Kevin M. Hayward, Nicholas K. |
author_sort | Aoude, Lauren G. |
collection | PubMed |
description | Partner and localizer of BRCA2 (PALB2) interacts with BRCA2 to enable double strand break repair through homologous recombination. Similar to BRCA2, germline mutations in PALB2 have been shown to predispose to Fanconi anaemia as well as pancreatic and breast cancer. The PALB2/BRCA2 protein interaction, as well as the increased melanoma risk observed in families harbouring BRCA2 mutations, makes PALB2 a candidate for melanoma susceptibility. In order to assess PALB2 as a melanoma predisposition gene, we sequenced the entire protein-coding sequence of PALB2 in probands from 182 melanoma families lacking pathogenic mutations in known high penetrance melanoma susceptibility genes: CDKN2A, CDK4, and BAP1. In addition, we interrogated whole-genome and exome data from another 19 kindreds with a strong family history of melanoma for deleterious mutations in PALB2. Here we report a rare known deleterious PALB2 mutation (rs118203998) causing a premature truncation of the protein (p.Y1183X) in an individual who had developed four different cancer types, including melanoma. Three other family members affected with melanoma did not carry the variant. Overall our data do not support a case for PALB2 being associated with melanoma predisposition. |
format | Online Article Text |
id | pubmed-4065098 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-40650982014-06-25 Assessment of PALB2 as a Candidate Melanoma Susceptibility Gene Aoude, Lauren G. Xu, Mai Zhao, Zhen Zhen Kovacs, Michael Palmer, Jane M. Johansson, Peter Symmons, Judith Trent, Jeffrey M. Martin, Nicholas G. Montgomery, Grant W. Brown, Kevin M. Hayward, Nicholas K. PLoS One Research Article Partner and localizer of BRCA2 (PALB2) interacts with BRCA2 to enable double strand break repair through homologous recombination. Similar to BRCA2, germline mutations in PALB2 have been shown to predispose to Fanconi anaemia as well as pancreatic and breast cancer. The PALB2/BRCA2 protein interaction, as well as the increased melanoma risk observed in families harbouring BRCA2 mutations, makes PALB2 a candidate for melanoma susceptibility. In order to assess PALB2 as a melanoma predisposition gene, we sequenced the entire protein-coding sequence of PALB2 in probands from 182 melanoma families lacking pathogenic mutations in known high penetrance melanoma susceptibility genes: CDKN2A, CDK4, and BAP1. In addition, we interrogated whole-genome and exome data from another 19 kindreds with a strong family history of melanoma for deleterious mutations in PALB2. Here we report a rare known deleterious PALB2 mutation (rs118203998) causing a premature truncation of the protein (p.Y1183X) in an individual who had developed four different cancer types, including melanoma. Three other family members affected with melanoma did not carry the variant. Overall our data do not support a case for PALB2 being associated with melanoma predisposition. Public Library of Science 2014-06-20 /pmc/articles/PMC4065098/ /pubmed/24949998 http://dx.doi.org/10.1371/journal.pone.0100683 Text en © 2014 Aoude et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Aoude, Lauren G. Xu, Mai Zhao, Zhen Zhen Kovacs, Michael Palmer, Jane M. Johansson, Peter Symmons, Judith Trent, Jeffrey M. Martin, Nicholas G. Montgomery, Grant W. Brown, Kevin M. Hayward, Nicholas K. Assessment of PALB2 as a Candidate Melanoma Susceptibility Gene |
title | Assessment of PALB2 as a Candidate Melanoma Susceptibility Gene |
title_full | Assessment of PALB2 as a Candidate Melanoma Susceptibility Gene |
title_fullStr | Assessment of PALB2 as a Candidate Melanoma Susceptibility Gene |
title_full_unstemmed | Assessment of PALB2 as a Candidate Melanoma Susceptibility Gene |
title_short | Assessment of PALB2 as a Candidate Melanoma Susceptibility Gene |
title_sort | assessment of palb2 as a candidate melanoma susceptibility gene |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4065098/ https://www.ncbi.nlm.nih.gov/pubmed/24949998 http://dx.doi.org/10.1371/journal.pone.0100683 |
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