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

Cytogenetic analysis of short-term cultures from colorectal adenomas revealed acquired clonal chromosome aberrations in 14 of 17 tumors. In 4 adenomas, only numerical changes were found, whereas 10 had structural rearrangements. Trisomy 7 was found as the sole change in one of the tumors and together with other numerical changes in another. A +7 was also present in one case with structural aberrations. Other recurrent numerical aberrations were -14 and -18, both found in 2 adenomas with structural karyotypic changes; in addition, one chromosome 14 was lost in one of the tumors with only numerical changes. The chromosome most often involved in structural aberrations was chromosome 1. In 6 cases, the rearrangements led to changes in I p, always with loss of material. The breakpoints were at 1p32-36. One adenoma had deletion of I p as the only change. Other chromosomes that were involved in changes in more than 2 cases were chromosomes 8, 13, and 17. These rearrangements typically led to gain of 8q and 13q and loss of 17p. The adenomas with structural abnormalities were generally larger and had a higher degree of dysplasia than did the adenomas with numerical changes only or those with a normal karyotype. All adenomas with a tubulovillous or villous architecture had structural rearrangements. Our findings confirm that a subset of colorectal adenomas exists that have only numerical chromosome aberrations. They also support our previous conclusion that loss of material from distal Ip is an early event in colorectal tumorigenesis, but that other cytogenetic aberrations follow and typically are present already at the adenomatous stage. The accumulation of chromosome-level mutational events in adenomas correlates with the pathologic features: the more malignancy-like the phenotype, the more complex the karyotype. There seems to be no single aberration that distinguishes colorectal adenomas from carcinomas, however. (C) 1994 Wiley-Liss, Inc.