CLONAL KARYOTYPIC ABNORMALITIES IN COLORECTAL ADENOMAS - CLUES TO THEEARLY GENETIC EVENTS IN THE ADENOMA-CARCINOMA SEQUENCE

Cytogenetic analysis of short-term cultures from colorectal adenomas r evealed acquired clonal chromosome aberrations in 14 of 17 tumors. In 4 adenomas, only numerical changes were found, whereas 10 had structur al rearrangements. Trisomy 7 was found as the sole change in one of th e tumors and together with other numerical changes in another. A +7 wa s also present in one case with structural aberrations. Other recurren t numerical aberrations were -14 and -18, both found in 2 adenomas wit h structural karyotypic changes; in addition, one chromosome 14 was lo st in one of the tumors with only numerical changes. The chromosome mo st often involved in structural aberrations was chromosome 1. In 6 cas es, the rearrangements led to changes in I p, always with loss of mate rial. The breakpoints were at 1p32-36. One adenoma had deletion of I p as the only change. Other chromosomes that were involved in changes i n more than 2 cases were chromosomes 8, 13, and 17. These rearrangemen ts typically led to gain of 8q and 13q and loss of 17p. The adenomas w ith structural abnormalities were generally larger and had a higher de gree of dysplasia than did the adenomas with numerical changes only or those with a normal karyotype. All adenomas with a tubulovillous or v illous architecture had structural rearrangements. Our findings confir m that a subset of colorectal adenomas exists that have only numerical chromosome aberrations. They also support our previous conclusion tha t loss of material from distal Ip is an early event in colorectal tumo rigenesis, but that other cytogenetic aberrations follow and typically are present already at the adenomatous stage. The accumulation of chr omosome-level mutational events in adenomas correlates with the pathol ogic features: the more malignancy-like the phenotype, the more comple x the karyotype. There seems to be no single aberration that distingui shes colorectal adenomas from carcinomas, however. (C) 1994 Wiley-Liss , Inc.