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Distinct Genetic Alterations in Colorectal Cancer
BACKGROUND: Colon cancer (CRC) development often includes chromosomal instability (CIN) leading to amplifications and deletions of large DNA segments. Epidemiological, clinical, and cytogenetic studies showed that there are considerable differences between CRC tumors from African Americans (AAs) and...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2811180/ https://www.ncbi.nlm.nih.gov/pubmed/20126641 http://dx.doi.org/10.1371/journal.pone.0008879 |
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author | Ashktorab, Hassan Schäffer, Alejandro A. Daremipouran, Mohammad Smoot, Duane T. Lee, Edward Brim, Hassan |
author_facet | Ashktorab, Hassan Schäffer, Alejandro A. Daremipouran, Mohammad Smoot, Duane T. Lee, Edward Brim, Hassan |
author_sort | Ashktorab, Hassan |
collection | PubMed |
description | BACKGROUND: Colon cancer (CRC) development often includes chromosomal instability (CIN) leading to amplifications and deletions of large DNA segments. Epidemiological, clinical, and cytogenetic studies showed that there are considerable differences between CRC tumors from African Americans (AAs) and Caucasian patients. In this study, we determined genomic copy number aberrations in sporadic CRC tumors from AAs, in order to investigate possible explanations for the observed disparities. METHODOLOGY/PRINCIPAL FINDINGS: We applied genome-wide array comparative genome hybridization (aCGH) using a 105k chip to identify copy number aberrations in samples from 15 AAs. In addition, we did a population comparative analysis with aCGH data in Caucasians as well as with a widely publicized list of colon cancer genes (CAN genes). There was an average of 20 aberrations per patient with more amplifications than deletions. Analysis of DNA copy number of frequently altered chromosomes revealed that deletions occurred primarily in chromosomes 4, 8 and 18. Chromosomal duplications occurred in more than 50% of cases on chromosomes 7, 8, 13, 20 and X. The CIN profile showed some differences when compared to Caucasian alterations. CONCLUSIONS/SIGNIFICANCE: Chromosome X amplification in male patients and chromosomes 4, 8 and 18 deletions were prominent aberrations in AAs. Some CAN genes were altered at high frequencies in AAs with EXOC4, EPHB6, GNAS, MLL3 and TBX22 as the most frequently deleted genes and HAPLN1, ADAM29, SMAD2 and SMAD4 as the most frequently amplified genes. The observed CIN may play a distinctive role in CRC in AAs. |
format | Text |
id | pubmed-2811180 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-28111802010-02-02 Distinct Genetic Alterations in Colorectal Cancer Ashktorab, Hassan Schäffer, Alejandro A. Daremipouran, Mohammad Smoot, Duane T. Lee, Edward Brim, Hassan PLoS One Research Article BACKGROUND: Colon cancer (CRC) development often includes chromosomal instability (CIN) leading to amplifications and deletions of large DNA segments. Epidemiological, clinical, and cytogenetic studies showed that there are considerable differences between CRC tumors from African Americans (AAs) and Caucasian patients. In this study, we determined genomic copy number aberrations in sporadic CRC tumors from AAs, in order to investigate possible explanations for the observed disparities. METHODOLOGY/PRINCIPAL FINDINGS: We applied genome-wide array comparative genome hybridization (aCGH) using a 105k chip to identify copy number aberrations in samples from 15 AAs. In addition, we did a population comparative analysis with aCGH data in Caucasians as well as with a widely publicized list of colon cancer genes (CAN genes). There was an average of 20 aberrations per patient with more amplifications than deletions. Analysis of DNA copy number of frequently altered chromosomes revealed that deletions occurred primarily in chromosomes 4, 8 and 18. Chromosomal duplications occurred in more than 50% of cases on chromosomes 7, 8, 13, 20 and X. The CIN profile showed some differences when compared to Caucasian alterations. CONCLUSIONS/SIGNIFICANCE: Chromosome X amplification in male patients and chromosomes 4, 8 and 18 deletions were prominent aberrations in AAs. Some CAN genes were altered at high frequencies in AAs with EXOC4, EPHB6, GNAS, MLL3 and TBX22 as the most frequently deleted genes and HAPLN1, ADAM29, SMAD2 and SMAD4 as the most frequently amplified genes. The observed CIN may play a distinctive role in CRC in AAs. Public Library of Science 2010-01-26 /pmc/articles/PMC2811180/ /pubmed/20126641 http://dx.doi.org/10.1371/journal.pone.0008879 Text en Ashktorab 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 Ashktorab, Hassan Schäffer, Alejandro A. Daremipouran, Mohammad Smoot, Duane T. Lee, Edward Brim, Hassan Distinct Genetic Alterations in Colorectal Cancer |
title | Distinct Genetic Alterations in Colorectal Cancer |
title_full | Distinct Genetic Alterations in Colorectal Cancer |
title_fullStr | Distinct Genetic Alterations in Colorectal Cancer |
title_full_unstemmed | Distinct Genetic Alterations in Colorectal Cancer |
title_short | Distinct Genetic Alterations in Colorectal Cancer |
title_sort | distinct genetic alterations in colorectal cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2811180/ https://www.ncbi.nlm.nih.gov/pubmed/20126641 http://dx.doi.org/10.1371/journal.pone.0008879 |
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