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Intrachromosomal Genomic Instability in Human Sporadic Colorectal Cancer Measured by Genome-Wide Allelotyping and Inter-(Simple Sequence Repeat) PCR¹

Departments of Cancer Genetics [G. R. A., W. M. H., J. M. C., M. J. K., N. C., J. D. B., J. K. B., G. P. J., N. J. N., T. B. S.], Surgical Oncology [G. R. A., B. M. B., M. A. R-B., N. J. P.], Cancer Prevention, Epidemiology and Biostatistics [H. S.], Clinical Cytogenetics [S. S.], and Experimental Pathology [D. L. S.], Roswell Park Cancer Institute, Buffalo, New York 14263; Department of Leukemia, M. D. Anderson Cancer Center, Houston, Texas 77030 [J-P. I.]; Department of Surgery, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229 [M. S. K.]; and University of Montreal Hospital Center, Montreal, Quebec, H2W 1T8 Canada [M. B.]

We have used genome-wide allelotyping with 348 polymorphic autosomal markers spaced, on average, 10 cM apart to quantitate the extent of intrachromosomal instability in 59 human sporadic colorectal carcinomas. We have compared instability measured by this method with that measured by inter-(simple sequence repeat) PCR and microsatellite instability assays. Instability quantitated by fractional allelic loss rates was found to be independent of that detected by microsatellite instability analyses but was weakly associated with that measured by inter-(simple sequence repeat) PCR. A set of seven loci were identified that were most strongly associated with elevated rates of fractional allelic loss and/or inter-(simple sequence repeat) PCR instability; these seven loci were on chromosomes 3, 8, 11, 13, 14, 18, and 20. A lesser association was seen with two loci flanking p53 on chromosome 17. Coordinate loss patterns for these loci suggest that at least two separate sets of cooperating loci exist for intrachromosomal genomic instability in human colorectal cancer.

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				H. Rubin and G. R. Anderson Correspondence re: G. Anderson et al., Intrachromosomal Genomic Instability in Human Sporadic Colorectal Cancer Measured by Genome-Wide Allelotyping and Inter-(Simple Sequence Repeat) PCR. Cancer Res., 61: 8274-8283, 2001. Cancer Res., November 1, 2002; 62(21): 6350 - 6351. [Full Text] [PDF]