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Association between Genetic Subgroups of Pancreatic Ductal Adenocarcinoma Defined by High Density 500 K SNP-Arrays and Tumor Histopathology
The specific genes and genetic pathways associated with pancreatic ductal adenocarcinoma are still largely unknown partially due to the low resolution of the techniques applied so far to their study. Here we used high-density 500 K single nucleotide polymorphism (SNP)-arrays to define those chromoso...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3141022/ https://www.ncbi.nlm.nih.gov/pubmed/21811587 http://dx.doi.org/10.1371/journal.pone.0022315 |
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author | Gutiérrez, María Laura Muñoz-Bellvis, Luís Abad, María del Mar Bengoechea, Oscar González-González, María Orfao, Alberto Sayagués, José María |
author_facet | Gutiérrez, María Laura Muñoz-Bellvis, Luís Abad, María del Mar Bengoechea, Oscar González-González, María Orfao, Alberto Sayagués, José María |
author_sort | Gutiérrez, María Laura |
collection | PubMed |
description | The specific genes and genetic pathways associated with pancreatic ductal adenocarcinoma are still largely unknown partially due to the low resolution of the techniques applied so far to their study. Here we used high-density 500 K single nucleotide polymorphism (SNP)-arrays to define those chromosomal regions which most commonly harbour copy number (CN) alterations and loss of heterozygozity (LOH) in a series of 20 PDAC tumors and we correlated the corresponding genetic profiles with the most relevant clinical and histopathological features of the disease. Overall our results showed that primary PDAC frequently display (>70%) extensive gains of chromosomes 1q, 7q, 8q and 20q, together with losses of chromosomes 1p, 9p, 12q, 17p and 18q, such chromosomal regions harboring multiple cancer- and PDAC-associated genes. Interestingly, these alterations clustered into two distinct genetic profiles characterized by gains of the 2q14.2, 3q22.1, 5q32, 10q26.13, 10q26.3, 11q13.1, 11q13.3, 11q13.4, 16q24.1, 16q24.3, 22q13.1, 22q13.31 and 22q13.32 chromosomal regions (group 1; n = 9) versus gains at 1q21.1 and losses of the 1p36.11, 6q25.2, 9p22.1, 9p24.3, 17p13.3 and Xp22.33 chromosomal regions (group 2; n = 11). From the clinical and histopathological point of view, group 1 cases were associated with smaller and well/moderately-differentiated grade I/II PDAC tumors, whereas and group 2 PDAC displayed a larger size and they mainly consisted of poorly-differentiated grade III carcinomas. These findings confirm the cytogenetic complexity and heterogenity of PDAC and provide evidence for the association between tumor cytogenetics and its histopathological features. In addition, we also show that the altered regions identified harbor multiple cancer associate genes that deserve further investigation to determine their relevance in the pathogenesis of PDAC. |
format | Online Article Text |
id | pubmed-3141022 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-31410222011-08-02 Association between Genetic Subgroups of Pancreatic Ductal Adenocarcinoma Defined by High Density 500 K SNP-Arrays and Tumor Histopathology Gutiérrez, María Laura Muñoz-Bellvis, Luís Abad, María del Mar Bengoechea, Oscar González-González, María Orfao, Alberto Sayagués, José María PLoS One Research Article The specific genes and genetic pathways associated with pancreatic ductal adenocarcinoma are still largely unknown partially due to the low resolution of the techniques applied so far to their study. Here we used high-density 500 K single nucleotide polymorphism (SNP)-arrays to define those chromosomal regions which most commonly harbour copy number (CN) alterations and loss of heterozygozity (LOH) in a series of 20 PDAC tumors and we correlated the corresponding genetic profiles with the most relevant clinical and histopathological features of the disease. Overall our results showed that primary PDAC frequently display (>70%) extensive gains of chromosomes 1q, 7q, 8q and 20q, together with losses of chromosomes 1p, 9p, 12q, 17p and 18q, such chromosomal regions harboring multiple cancer- and PDAC-associated genes. Interestingly, these alterations clustered into two distinct genetic profiles characterized by gains of the 2q14.2, 3q22.1, 5q32, 10q26.13, 10q26.3, 11q13.1, 11q13.3, 11q13.4, 16q24.1, 16q24.3, 22q13.1, 22q13.31 and 22q13.32 chromosomal regions (group 1; n = 9) versus gains at 1q21.1 and losses of the 1p36.11, 6q25.2, 9p22.1, 9p24.3, 17p13.3 and Xp22.33 chromosomal regions (group 2; n = 11). From the clinical and histopathological point of view, group 1 cases were associated with smaller and well/moderately-differentiated grade I/II PDAC tumors, whereas and group 2 PDAC displayed a larger size and they mainly consisted of poorly-differentiated grade III carcinomas. These findings confirm the cytogenetic complexity and heterogenity of PDAC and provide evidence for the association between tumor cytogenetics and its histopathological features. In addition, we also show that the altered regions identified harbor multiple cancer associate genes that deserve further investigation to determine their relevance in the pathogenesis of PDAC. Public Library of Science 2011-07-21 /pmc/articles/PMC3141022/ /pubmed/21811587 http://dx.doi.org/10.1371/journal.pone.0022315 Text en Gutiérrez 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 Gutiérrez, María Laura Muñoz-Bellvis, Luís Abad, María del Mar Bengoechea, Oscar González-González, María Orfao, Alberto Sayagués, José María Association between Genetic Subgroups of Pancreatic Ductal Adenocarcinoma Defined by High Density 500 K SNP-Arrays and Tumor Histopathology |
title | Association between Genetic Subgroups of Pancreatic Ductal Adenocarcinoma Defined by High Density 500 K SNP-Arrays and Tumor Histopathology |
title_full | Association between Genetic Subgroups of Pancreatic Ductal Adenocarcinoma Defined by High Density 500 K SNP-Arrays and Tumor Histopathology |
title_fullStr | Association between Genetic Subgroups of Pancreatic Ductal Adenocarcinoma Defined by High Density 500 K SNP-Arrays and Tumor Histopathology |
title_full_unstemmed | Association between Genetic Subgroups of Pancreatic Ductal Adenocarcinoma Defined by High Density 500 K SNP-Arrays and Tumor Histopathology |
title_short | Association between Genetic Subgroups of Pancreatic Ductal Adenocarcinoma Defined by High Density 500 K SNP-Arrays and Tumor Histopathology |
title_sort | association between genetic subgroups of pancreatic ductal adenocarcinoma defined by high density 500 k snp-arrays and tumor histopathology |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3141022/ https://www.ncbi.nlm.nih.gov/pubmed/21811587 http://dx.doi.org/10.1371/journal.pone.0022315 |
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