Association of survival and disease progression with chromosomal instability: A genomic exploration of colorectal cancer Journal Article
| Authors: | Sheffer, M.; Bacolod, M. D.; Zuk, O.; Giardina, S. F.; Pincas, H.; Barany, F.; Paty, P. B.; Gerald, W. L.; Notterman, D. A.; Domany, E. |
| Article Title: | Association of survival and disease progression with chromosomal instability: A genomic exploration of colorectal cancer |
| Abstract: | 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 VEGFA, MYC, MET, FGF6, FGF23, LYN. MMP9, MYBL2, AURKA, UBE2C. and PTEN. Other focal events encompassed potential new candidate tumor suppressors (losses) and oncogenes (gains), including CCDC68, CSMD1, POLR1D, and PMEPA1. 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. |
| Keywords: | survival; controlled study; human tissue; survival rate; unclassified drug; single nucleotide polymorphism; genetics; polymorphism, single nucleotide; disease course; cancer staging; colorectal cancer; adenocarcinoma; gene; metastasis; gene expression; gelatinase b; pathology; phosphorylation; colorectal carcinoma; colorectal neoplasms; gene expression regulation; genome analysis; gene expression regulation, neoplastic; statistical analysis; oligonucleotide array sequence analysis; disease progression; colorectal adenoma; colorectal tumor; colon cancer; human genome; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; vasculotropin a; chromosomal instability; dna microarray; gene dosage; untranslated rna; rna, untranslated; chromosome deletion; chromosome 18; oxidation reduction reaction; oxidation-reduction; oncogene myc; genome, human; chromosome 14q; chromosome 8q; scatter factor receptor; dna copy number; snp arrays; fibroblast growth factor 23; fibroblast growth factor 6; protein kinase lyn; ubiquitin conjugating enzyme; ubiquitin conjugating enzyme ube2c; aurka gene; chromosome 15q; chromosome 17p; chromosome 20p; chromosome 22q; chromosome 7; oncogene myb |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 106 |
| Issue: | 17 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2009-04-28 |
| Start Page: | 7131 |
| End Page: | 7136 |
| Language: | English |
| DOI: | 10.1073/pnas.0902232106 |
| PUBMED: | 19359472 |
| PROVIDER: | scopus |
| PMCID: | PMC2678450 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 5" - "Export Date: 30 November 2010" - "CODEN: PNASA" - "Source: Scopus" |
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