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Association between genomic alterations and metastatic behavior of colorectal cancer identified by array-based comparative genomic hybridization.
Genes Chromosomes Cancer 2013; 52(2):140-9GC

Abstract

Colorectal cancers (CRCs) exhibit multiple genetic alterations, including allelic imbalances (copy number alterations, CNAs) at various chromosomal loci. In addition to genetic aberrations, DNA methylation also plays important roles in the development of CRC. To better understand the clinical relevance of these genetic and epigenetic abnormalities in CRC, we performed an integrative analysis of copy number changes on a genome-wide scale and assessed mutations of TP53, KRAS, BRAF, and PIK3CA and DNA methylation of six marker genes in single glands isolated from 39 primary tumors. Array-based comparative genomic hybridization (array-CGH) analysis revealed that genomic losses commonly occurred at 3q26.1, 4q13.2, 6q21.32, 7q34, 8p12-23.3, 15qcen and 18, while gains were commonly found at 1q21.3-23.1, 7p22.3-q34, 13q12.11-14.11, and 20. The total numbers and lengths of the CNAs were significantly associated with the aberrant DNA methylation and Dukes' stages. Moreover, hierarchical clustering analysis of the array-CGH data suggested that tumors could be categorized into four subgroups. Tumors with frequent DNA methylation were most strongly enriched in subgroups with infrequent CNAs. Importantly, Dukes' D tumors were enriched in the subgroup showing the greatest genomic losses, whereas Dukes' C tumors were enriched in the subgroup with the greatest genomic gains. Our data suggest an inverse relationship between chromosomal instability and aberrant methylation and a positive association between genomic losses and distant metastasis and between genomic gains and lymph node metastasis in CRC. Therefore, DNA copy number profiles may be predictive of the metastatic behavior of CRCs.

Authors+Show Affiliations

Department of Molecular Biology, Sapporo Medical University, Sapporo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23073979

Citation

Sawada, Takeshi, et al. "Association Between Genomic Alterations and Metastatic Behavior of Colorectal Cancer Identified By Array-based Comparative Genomic Hybridization." Genes, Chromosomes & Cancer, vol. 52, no. 2, 2013, pp. 140-9.
Sawada T, Yamamoto E, Suzuki H, et al. Association between genomic alterations and metastatic behavior of colorectal cancer identified by array-based comparative genomic hybridization. Genes Chromosomes Cancer. 2013;52(2):140-9.
Sawada, T., Yamamoto, E., Suzuki, H., Nojima, M., Maruyama, R., Shioi, Y., ... Sugai, T. (2013). Association between genomic alterations and metastatic behavior of colorectal cancer identified by array-based comparative genomic hybridization. Genes, Chromosomes & Cancer, 52(2), pp. 140-9. doi:10.1002/gcc.22013.
Sawada T, et al. Association Between Genomic Alterations and Metastatic Behavior of Colorectal Cancer Identified By Array-based Comparative Genomic Hybridization. Genes Chromosomes Cancer. 2013;52(2):140-9. PubMed PMID: 23073979.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association between genomic alterations and metastatic behavior of colorectal cancer identified by array-based comparative genomic hybridization. AU - Sawada,Takeshi, AU - Yamamoto,Eiichiro, AU - Suzuki,Hiromu, AU - Nojima,Masanori, AU - Maruyama,Reo, AU - Shioi,Yoshihiro, AU - Akasaka,Risaburo, AU - Kamimae,Seiko, AU - Harada,Taku, AU - Ashida,Masami, AU - Kai,Masahiro, AU - Adachi,Yasushi, AU - Yamamoto,Hiroyuki, AU - Imai,Kohzoh, AU - Toyota,Minoru, AU - Itoh,Fumio, AU - Sugai,Tamotsu, Y1 - 2012/10/17/ PY - 2012/02/21/received PY - 2012/08/22/accepted PY - 2012/10/18/entrez PY - 2012/10/18/pubmed PY - 2013/5/25/medline SP - 140 EP - 9 JF - Genes, chromosomes & cancer JO - Genes Chromosomes Cancer VL - 52 IS - 2 N2 - Colorectal cancers (CRCs) exhibit multiple genetic alterations, including allelic imbalances (copy number alterations, CNAs) at various chromosomal loci. In addition to genetic aberrations, DNA methylation also plays important roles in the development of CRC. To better understand the clinical relevance of these genetic and epigenetic abnormalities in CRC, we performed an integrative analysis of copy number changes on a genome-wide scale and assessed mutations of TP53, KRAS, BRAF, and PIK3CA and DNA methylation of six marker genes in single glands isolated from 39 primary tumors. Array-based comparative genomic hybridization (array-CGH) analysis revealed that genomic losses commonly occurred at 3q26.1, 4q13.2, 6q21.32, 7q34, 8p12-23.3, 15qcen and 18, while gains were commonly found at 1q21.3-23.1, 7p22.3-q34, 13q12.11-14.11, and 20. The total numbers and lengths of the CNAs were significantly associated with the aberrant DNA methylation and Dukes' stages. Moreover, hierarchical clustering analysis of the array-CGH data suggested that tumors could be categorized into four subgroups. Tumors with frequent DNA methylation were most strongly enriched in subgroups with infrequent CNAs. Importantly, Dukes' D tumors were enriched in the subgroup showing the greatest genomic losses, whereas Dukes' C tumors were enriched in the subgroup with the greatest genomic gains. Our data suggest an inverse relationship between chromosomal instability and aberrant methylation and a positive association between genomic losses and distant metastasis and between genomic gains and lymph node metastasis in CRC. Therefore, DNA copy number profiles may be predictive of the metastatic behavior of CRCs. SN - 1098-2264 UR - https://www.unboundmedicine.com/medline/citation/23073979/Association_between_genomic_alterations_and_metastatic_behavior_of_colorectal_cancer_identified_by_array_based_comparative_genomic_hybridization_ L2 - https://doi.org/10.1002/gcc.22013 DB - PRIME DP - Unbound Medicine ER -