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Comprehensive Genomic Analysis of a BRCA2 Deficient Human Pancreatic Cancer

Capan-1 is a well-characterised BRCA2-deficient human cell line isolated from a liver metastasis of a pancreatic adenocarcinoma. Here we report a genome-wide assessment of structural variations and high-depth exome characterization of single nucleotide variants and small insertion/deletions in Capan...

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Autores principales: Barber, Louise J., Rosa Rosa, Juan M., Kozarewa, Iwanka, Fenwick, Kerry, Assiotis, Ioannis, Mitsopoulos, Costas, Sims, David, Hakas, Jarle, Zvelebil, Marketa, Lord, Christopher J., Ashworth, Alan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3130048/
https://www.ncbi.nlm.nih.gov/pubmed/21750719
http://dx.doi.org/10.1371/journal.pone.0021639
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author Barber, Louise J.
Rosa Rosa, Juan M.
Kozarewa, Iwanka
Fenwick, Kerry
Assiotis, Ioannis
Mitsopoulos, Costas
Sims, David
Hakas, Jarle
Zvelebil, Marketa
Lord, Christopher J.
Ashworth, Alan
author_facet Barber, Louise J.
Rosa Rosa, Juan M.
Kozarewa, Iwanka
Fenwick, Kerry
Assiotis, Ioannis
Mitsopoulos, Costas
Sims, David
Hakas, Jarle
Zvelebil, Marketa
Lord, Christopher J.
Ashworth, Alan
author_sort Barber, Louise J.
collection PubMed
description Capan-1 is a well-characterised BRCA2-deficient human cell line isolated from a liver metastasis of a pancreatic adenocarcinoma. Here we report a genome-wide assessment of structural variations and high-depth exome characterization of single nucleotide variants and small insertion/deletions in Capan-1. To identify potential somatic and tumour-associated variations in the absence of a matched-normal cell line, we devised a novel method based on the analysis of HapMap samples. We demonstrate that Capan-1 has one of the most rearranged genomes sequenced to date. Furthermore, small insertions and deletions are detected more frequently in the context of short sequence repeats than in other genomes. We also identify a number of novel mutations that may represent genetic changes that have contributed to tumour progression. These data provide insight into the genomic effects of loss of BRCA2 function.
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spelling pubmed-31300482011-07-12 Comprehensive Genomic Analysis of a BRCA2 Deficient Human Pancreatic Cancer Barber, Louise J. Rosa Rosa, Juan M. Kozarewa, Iwanka Fenwick, Kerry Assiotis, Ioannis Mitsopoulos, Costas Sims, David Hakas, Jarle Zvelebil, Marketa Lord, Christopher J. Ashworth, Alan PLoS One Research Article Capan-1 is a well-characterised BRCA2-deficient human cell line isolated from a liver metastasis of a pancreatic adenocarcinoma. Here we report a genome-wide assessment of structural variations and high-depth exome characterization of single nucleotide variants and small insertion/deletions in Capan-1. To identify potential somatic and tumour-associated variations in the absence of a matched-normal cell line, we devised a novel method based on the analysis of HapMap samples. We demonstrate that Capan-1 has one of the most rearranged genomes sequenced to date. Furthermore, small insertions and deletions are detected more frequently in the context of short sequence repeats than in other genomes. We also identify a number of novel mutations that may represent genetic changes that have contributed to tumour progression. These data provide insight into the genomic effects of loss of BRCA2 function. Public Library of Science 2011-07-05 /pmc/articles/PMC3130048/ /pubmed/21750719 http://dx.doi.org/10.1371/journal.pone.0021639 Text en Barber 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
Barber, Louise J.
Rosa Rosa, Juan M.
Kozarewa, Iwanka
Fenwick, Kerry
Assiotis, Ioannis
Mitsopoulos, Costas
Sims, David
Hakas, Jarle
Zvelebil, Marketa
Lord, Christopher J.
Ashworth, Alan
Comprehensive Genomic Analysis of a BRCA2 Deficient Human Pancreatic Cancer
title Comprehensive Genomic Analysis of a BRCA2 Deficient Human Pancreatic Cancer
title_full Comprehensive Genomic Analysis of a BRCA2 Deficient Human Pancreatic Cancer
title_fullStr Comprehensive Genomic Analysis of a BRCA2 Deficient Human Pancreatic Cancer
title_full_unstemmed Comprehensive Genomic Analysis of a BRCA2 Deficient Human Pancreatic Cancer
title_short Comprehensive Genomic Analysis of a BRCA2 Deficient Human Pancreatic Cancer
title_sort comprehensive genomic analysis of a brca2 deficient human pancreatic cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3130048/
https://www.ncbi.nlm.nih.gov/pubmed/21750719
http://dx.doi.org/10.1371/journal.pone.0021639
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