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Dissecting Karyotypic Patterns in Colorectal Tumors

Two Distinct but Overlapping Pathways in the Adenoma-Carcinoma Transition¹

Department of Clinical Genetics, University Hospital, SE-221 85 Lund, Sweden [M. H., D. G., G. B. H., F. M.]; Department of Genetics, Lund University, SE-223 62 Lund, Sweden [T. S.]; and Department of Oncology, the Jubileum Institution, University Hospital, SE-221 85 Lund, Sweden [M. N.]

More than 500 colorectal tumors with clonal chromosomal abnormalities have been reported. Although the pattern of aberrations is nonrandom, no specific primary or secondary karyotypic abnormality has been identified. Also, the chronological order in which the aberrations appear during disease progression is not well known. One reason why our understanding of the cytogenetic evolution is unclear is the high degree of karyotypic complexity seen in these tumors. To overcome some of these difficulties we have previously used several statistical methods that allow identification and interpretation of karyotypic pathways as well as establishment of a temporal order of appearance of the imbalances. These methods were applied on 531 colorectal tumor karyotypes. By using a resampling strategy, 1p-, +7, 7q-, and +12p were identified as early events. Two major and two minor cytogenetic pathways were identified by means of principal component analysis. The two major pathways were initiated with 1p- and +7, and the minor pathways were initiated with +12p and 7q-. The +7/+12p tumors were found to be hyperdiploid, whereas those with 1p-/7q- were pseudodiploid. We also show that the adenoma-carcinoma transition in the 1p- pathway is strongly linked to karyoytypic evolution, whereas the +7 pathway is not, and that the cytogenetic pathways are separated at both early and late stages.

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