Association of survival and disease progression with chromosomal instability: A genomic exploration of colorectal cancer Export

@article{citeulike:4306482, abstract = {10.1073/pnas.0902232106 During disease progression the cells that comprise solid malignancies undergo significant changes in gene copy number and chromosome structure. Colorectal cancer provides an excellent model to study this process. To indentify and characterize chromosomal abnormalities in colorectal cancer, we performed a statistical analysis of 299 expression and 130 SNP arrays profiled at different stages of the disease, including normal tissue, adenoma, stages 1\^{a}€“4 adenocarcinoma, and metastasis. We identified broad (> 1/2 chromosomal arm) and focal (< 1/2 chromosomal arm) events. Broad amplifications were noted on chromosomes 7, 8q, 13q, 20, and X and broad deletions on chromosomes 4, 8p, 14q, 15q, 17p, 18, 20p, and 22q. Focal events (gains or losses) were identified in regions containing known cancer pathway genes, such as , , , , , , , , , , and . Other focal events encompassed potential new candidate tumor suppressors (losses) and oncogenes (gains), including , , , and . From the expression data, we identified genes whose expression levels reflected their copy number changes and used this relationship to impute copy number changes to samples without accompanying SNP data. This analysis provided the statistical power to show that deletions of 8p, 4p, and 15q are associated with survival and disease progression, and that samples with simultaneous deletions in 18q, 8p, 4p, and 15q have a particularly poor prognosis. Annotation analysis reveals that the oxidative phosphorylation pathway shows a strong tendency for decreased expression in the samples characterized by poor prognosis.}, author = {Sheffer, Michal and Bacolod, Manny D. and Zuk, Or and Giardina, Sarah F. and Pincas, Hanna and Barany, Francis and Paty, Philip B. and Gerald, William L. and Notterman, Daniel A. and Domany, Eytan}, citeulike-article-id = {4306482}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0902232106}, citeulike-linkout-1 = {http://www.pnas.org/content/106/17/7131.abstract}, citeulike-linkout-2 = {http://www.pnas.org/content/106/17/7131.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/19359472}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=19359472}, day = {28}, doi = {10.1073/pnas.0902232106}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, keywords = {colon\_cancer, copy-number, survival}, month = {April}, number = {17}, pages = {7131--7136}, posted-at = {2009-11-08 23:03:53}, priority = {5}, title = {Association of survival and disease progression with chromosomal instability: A genomic exploration of colorectal cancer}, url = {http://dx.doi.org/10.1073/pnas.0902232106}, volume = {106}, year = {2009} }

TY - JOUR ID - citeulike:4306482 L3 - citeulike-article-id:4306482 N2 - 10.1073/pnas.0902232106 During disease progression the cells that comprise solid malignancies undergo significant changes in gene copy number and chromosome structure. Colorectal cancer provides an excellent model to study this process. To indentify and characterize chromosomal abnormalities in colorectal cancer, we performed a statistical analysis of 299 expression and 130 SNP arrays profiled at different stages of the disease, including normal tissue, adenoma, stages 1–4 adenocarcinoma, and metastasis. We identified broad (> 1/2 chromosomal arm) and focal (< 1/2 chromosomal arm) events. Broad amplifications were noted on chromosomes 7, 8q, 13q, 20, and X and broad deletions on chromosomes 4, 8p, 14q, 15q, 17p, 18, 20p, and 22q. Focal events (gains or losses) were identified in regions containing known cancer pathway genes, such as , , , , , , , , , , and . Other focal events encompassed potential new candidate tumor suppressors (losses) and oncogenes (gains), including , , , and . From the expression data, we identified genes whose expression levels reflected their copy number changes and used this relationship to impute copy number changes to samples without accompanying SNP data. This analysis provided the statistical power to show that deletions of 8p, 4p, and 15q are associated with survival and disease progression, and that samples with simultaneous deletions in 18q, 8p, 4p, and 15q have a particularly poor prognosis. Annotation analysis reveals that the oxidative phosphorylation pathway shows a strong tendency for decreased expression in the samples characterized by poor prognosis. IS - 17 JF - Proceedings of the National Academy of Sciences SN - 1091-6490 EP - 7136 TI - Association of survival and disease progression with chromosomal instability: A genomic exploration of colorectal cancer VL - 106 SP - 7131 KW - colon_cancer KW - copy-number KW - survival AU - Sheffer, Michal AU - Bacolod, Manny AU - Zuk, Or AU - Giardina, Sarah AU - Pincas, Hanna AU - Barany, Francis AU - Paty, Philip AU - Gerald, William AU - Notterman, Daniel AU - Domany, Eytan PY - 2009/04/28/ UR - http://dx.doi.org/10.1073/pnas.0902232106 ER -