Analysis of chromosomal instability in human colorectal adenomas with two mutational hits at APC

摘要: In vitro data show that the adenomatous polyposis coli (APC) protein associates with mitotic spindle and mouse embryonic stem cells biallelic Apc mutations are karyotypically unstable. These findings led to suggestions APC acts in chromosomal segregation inactivation leads instability (CIN). An alternative hypothesis based on allelic loss studies colorectal adenomas proposes CIN precedes contributes genetic changes at APC. We determined whether two features consistent these models by studying 55 lesions (average size 5 mm; range 1–13 mm) from patients familial polyposis. A variety of methods was used depending available material, including flow cytometry, comparative genomic hybridization, heterozygosity (LOH) analysis. Selected were assessed for proliferative activity Ki-67 immunocytochemistry. Seventeen 20 (85%) tumors diploid, near-diploid, one hypotetraploid. Just (near-diploid) tumor showed increased activity. LOH found occasionally chromosome 15q (2 49 tumors), but not 18q (0 48). adenomas, associated 5q 5p markers, former encompassing a minimum Mb. However, three analyzed hybridization displayed normal profiles, suggesting, together other data, mechanism is probably somatic recombination. Our results therefore do support tumorigenesis. Regarding model which lead directly CIN, if have this effect vivo, it must be subtle. Alternatively, might essentially an phenomenon.