Genome-wide allelotyping of 104 Finnish colorectal cancers reveals an excess of allelic imbalance in chromosome 20q in familial cases.
Laiho P., Hienonen T., Karhu A., Lipton L., Aalto Y., Thomas HJW., Birkenkamp-Demtroder K., Hodgson S., Salovaara R., Mecklin J-P., Järvinen H., Knuutila S., Halford S., Ørntoft TF., Tomlinson I., Launonen V., Houlston R., Aaltonen LA.
We have allelotyped a series of 104 Finnish colorectal cancers (CRCs) using 372 polymorphic markers spaced, on average, at 10 cM intervals, and have made a comparison of the differences in the frequency of allelic imbalance (AI) between familial and sporadic cases. Differences in the frequency of allelic imbalance (loss of heterozygosity or amplification) at a number of loci were detected and these were evaluated through analysis of additional series of cancers using specific markers. The most consistent difference was observed at chromosome 20q13.1-13.3 characterized by a two fold difference between familial and nonfamilial disease in a total of 99 familial and 186 sporadic Finnish cases. This difference was not observed in a UK set of 67 familial and 96 sporadic CRCs. The genome-wide effort resulted in a large data set giving clues to the location of putative CRC predisposition genes in the genome. The approach provides an alternative strategy for detecting cancer predisposition genes solely reliant on the molecular analysis of single cases obviating the requirement to collect multiple samples from families.