Frequent Allelic Imbalance on Chromosome 18q21 in Early Superficial Colorectal Cancers

Abstract

Genetic alterations in early superficial colorectal cancers have rarely been reported. In the present study, we searched for alterations in the APC and p53 genes in 27 superficial (20 depressed and 7 elevated) and 21 protruding colorectal cancers with submucosal invasion by means of PCR-single strand conformation polymorphism. Allelic imbalance (AI) on five loci, i.e., 1p34-36, 8p21-22, 14q32, 18q21 and 22q12-13, was also analyzed. Since a high incidence of 18q21 AI was detected in the superficial depressed cases, we further screened for alterations in Smad2, Smad4 and DCC. APC alterations were observed in three superficial depressed, one superficial elevated, and 11 protruding colorectal cancers, indicating that the frequency of APC alterations in superficial depressed cases was significantly lower than that in the protruding ones. There was no significant association between p53 alterations and macroscopic types. AI on 18q21 (13/20, 65%) was much higher than those on the other four loci in the superficial depressed cases. Moreover, the frequency of 18q21 AI in the superficial depressed cases was significantly higher than that in the protruding ones. Smad4 alterations were only detected in 1 of the 13 superficial depressed and 3 of the 17 protruding cases, while Smad2 and DCC alterations were not detected in any case examined. These data suggest that the carcinogenetic pathways of protruding and superficial depressed colorectal cancers are different, and that alterations of tumor suppressor gene(s) located on 18q21 other than Smad2, Smad4 and DCC might be associated with most superficial depressed colorectal cancers.

Down‐regulation of drs mRNA in Colorectal Neoplasms

“…[24][25][26][27] In contrast, the frequency of APC alterations in superficial depressed tumors has been shown to be significantly lower than that in protruding ones, and mutant K-ras is associated with polypoid growth carcinomas rather than non-polypoid growth carcinomas. 28) The superficial-type colorectal tumors are etiologically distinct from ordinary colorectal polypoid tumors and therefore may follow an alternative colorectal tumorigenesis pathway. 29) Inoue et al have previously reported that drs has the ability to suppress v-src and v-K-ras transformation without disturbing cell proliferation in the rat cell line F2408, 5) and Yamashita et al have reported that induction of the drs gene in colon cancer cell lines causes suppression of anchorage-independent growth of these cells.…”

Genomic organization of human arylamine N-acetyltransferase Type I reveals alternative promoters that generate different 5′-UTR splice variants with altered translational activities

“…Human NAT1 (arylamine N-acetyltransferase Type I; EC 2.3.1.5) is found in most tissues, where it catalyses the transfer of an acetyl group from acetyl-CoA to arylamine and hydrazine substrates [1][2][3], including the folate catabolite p-aminobenzoylglutamate [4,5]. The gene encoding NAT1 is genetically variant, and is located at 8p21.3-22, a site that is often deleted in human tumours [6][7][8][9]. A second gene (NAT2; arylamine N-acetyltransferase Type 2) that shares high sequence identity with NAT1 is located approx.…”

Loss of Dpc4 Expression in Colonic Adenocarcinomas Correlates with the Presence of Metastatic Disease

“…MacGrogan et al 29 described altered DPC4 sequences in three of 12 colon cancer cell lines and one of five primary tumors, whereas Takagi et al 30 found mutations of DPC4 in five of 31 (16%) primary tumors. Akiyama et al 31 described DPC4 alterations in four of 30 (13%) of early superficial colorectal cancers; interestingly none of their cases harbored either DCC or smad2 alterations, despite a 65% frequency of LOH at 18q21. Similarly, Koyama et al, 32 who found no more than seven of 64 (11%) of tumors with DPC4 mutations despite a 78% LOH at 18q21 in their stage II and III colorectal cancers.…”