Comparative genomic hybridization reveals a specific pattern of chromosomal gains and losses during the genesis of colorectal tumors

Abstract

Comparative genomic hybridization was used to screen the DNA extracted from histologically defined tissue sections from consecutive stages of colorectal carcinogenesis for chromosomal aberrations. No aberrations were detected in normal epithelium (n = 14). Gain of chromosome 7 occurred as a single event in low‐grade adenomas (n = 14). In high‐grade adenomas (n = 12), an overrepresentation of chromosomes 7 and 20 was present in 30% of the cases analyzed. The transition to colon carcinomas (n = 16) was characterized by the emergence of multiple chromosomal aberrations. Chromosomes 1, 13, and 20 and chromosome arms 7p and 8q were frequently gained, whereas chromosome 4 and chromosome arms 8p and 18q were recurrently underrepresented. The same tissue sections that were used for CGH were analyzed by means of DNA‐ploidy measurements and immunohistochemical staining to quantify proliferative activity and p21/WAF‐I and TP53 expression. We observed that crude aneuploidy and increased proliferative activity are early events in colorectal carcinogenesis, followed by TP53 overexpression and the acquisition of recurrent chromosomal gains and losses during the progression from high‐grade adenomas to invasive carcinomas. Genes Chromosom Cancer (1996). © 1996 Wiley‐Liss, Inc.

Overexpression of E2F-1 in Lung and Liver Metastases of Human Colon Cancer is Associated with Gene Amplification

“…It was striking to note that 16 of the 18 metastatic tumor samples had gains in chromosome 20 or gains specific to 20q, in as much as E2F-1 has been mapped to 20q11.2, 18 and chromosome 20 and regions in the 20q arm have been shown to be amplified in colorectal tumor samples as well as other human carcinomas and adenomas. [19][20][21][22][23][24][25][26][27] This is further supported by our DNA PCR data for the increase in gene copy number of E2F-1 in these metastatic colon tumor samples (Fig. 1).…”

Overexpression of EIF5A2 promotes colorectal carcinoma cell aggressiveness by upregulating MTA1 through C-myc to induce epithelial–mesenchymaltransition

“…Amplification of 3q is one of the most frequent chromosomal aberrations in CRC6 7 and many other human cancers including ovarian,8 lung,9 oesophageal,10 gastric,11 cervical12 and prostate13 carcinomas. These imply that human chromosome 3q contains oncogenes related to the tumorigenesis and/or progression of human cancers.…”

Telomere shortening of epithelial cells characterises the adenoma-carcinoma transition of human colorectal cancer

“…Additional support for this hypothesis derives from studies on the prevalence of CIN showing a sharp increase in aneuploidy at the adenoma-carcinoma transition. [5][6][7][8][9][10][11][12][13][14] According to the telomere hypothesis of cancer initiation, CIN induced by critical telomere shortening and loss of telomere function triggers the genetic lesions necessary for cellular transformation. In line with the telomere hypothesis of cancer initiation, the rate of anaphase bridges-a sign of telomere dysfunction-sharply increases at this transition.…”

“…2 CIN sharply increases at the adenoma-carcinoma transition. [5][6][7][8][9][10][11][12][13][14] Mutations in several genes governing mitotic 15 and cell cycle checkpoints (for example, p53) 16 have been linked to the onset of CIN at the adenoma-carcinoma transition but the mechanisms leading to the CIN phenotype have yet to be evaluated. One current hypothesis is that loss of telomere function triggers CIN thus leading to cancer initiation.…”