Clonal karyotypic abnormalities in colorectal adenomas: Clues to the early genetic events in the adenoma‐carcinoma sequence

Abstract

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 1p, always with loss of material. The breakpoints were at 1p32-36. One adenoma had deletion of 1p 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 1p is an early event in colorectal tumorigenesis, but that other cytogenetic aberrations follow and typically are present already at the adenomatous stage.(ABSTRACT TRUNCATED AT 250 WORDS)

Aneuploidy and Epithelial Cancers: The Impact of Aneuploidy on the Genesis, Progression and Prognosis of Colorectal and Breast Carcinomas

“…This suggests both an initial requirement for the acquisition of specific chromosomal aneuploidy and a requirement for the maintenance of these imbalances despite genomic and chromosomal instability. This would be consistent with continuous selective pressure to retain a specific pattern of chromosomal copy number changes in the majority of tumor cells (Bomme et al 1994;Ried et al 1999;Nowak et al 2002;Desper et al 2000). Chromosomal aneuploidy is also the earliest detectable genomic aberration in cell culture model systems in which cells are exposed to carcinogens or subject to spontaneous transformation (Barrett et al 1985;Padilla-Nash et al 2011).…”

Ulcerative Colitis and Colorectal Cancer: Aneuploidy and Implications for Improved Screening

“…This suggests that there is both an initial requirement for the acquisition of specific chromosomal aneuploidy and a requirement for the maintenance of these imbalances despite genomic and chromosomal instability. This would be consistent with continuous selective pressure to retain a specific pattern of chromosomal copy number changes in the majority of tumor cells (Bomme et al 1994;Ried et al 1999;Nowak et al 2002;Desper et al 2000). Additionally, in cell culture model systems in which cells are exposed to different carcinogens, chromosomal aneuploidy is the earliest detectable genomic aberration (Barrett et al 1985;Oshimura and Barrett 1986).…”

“…These aneuploidies result in a recurrent pattern of genomic imbalances, which is specific and conserved for these tumors . For instance, one of the earliest acquired genetic abnormalities during colorectal tumorigenesis are copy number gains of chromosome 7 (Bomme et al 1994). These trisomies can already be observed in benign polyps, and can emerge in otherwise stable, diploid genomes.…”

Genomic instability and oncogene amplifications in colorectal adenomas predict recurrence and synchronous carcinoma

“…nci.nih.gov/Chromosomes/Mitelman. Bomme et al 10 could show that such specific chromosomal aberrations -especially, a gain of chromosomes 7 and 13 -already exist in adenomas. These aberrations are faithfully conserved in carcinomas and are accompanied by gains of chromosomes and chromosomal arms 6, 8q, and 20, as well as losses of 4q, 8p, 17p, and 18q.…”