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

• Published in: Cancer science Vol. 90; no. 12; pp. 1329 - 1337
• Main Authors: Akiyama, Yoshimitsu, Arai, Takehiro, Nagasaki, Hiromi, Yagi, Osmar Kenji, Nakahata, Atsuko, Nakajima, Tomoko, Ohkura, Yasuo, Iwai, Takehisa, Saitoh, Kiyoshi, Yuasa, Yasuhito
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.12.1999; Japanese Cancer Association; John Wiley & Sons, Inc
• Subjects: Adenomatous polyposis coli; Adult; Aged; Aged, 80 and over; Alleles; Allelic imbalance; APC; Biological and medical sciences; Chromosome 1; Chromosome 18; Chromosomes, Human, Pair 18 - genetics; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Conformation; DNA-Binding Proteins - genetics; Early superficial colorectal cancer; Female; Gastroenterology. Liver. Pancreas. Abdomen; Genes, APC; Genes, DCC; Genes, p53; Humans; Male; Medical sciences; Microsatellite Repeats; Middle Aged; Mutation; p53 Protein; Smad2 Protein; Smad4 18q21; Smad4 Protein; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Trans-Activators - genetics; Tumor suppressor genes; Tumors; Chromosomal aberration; Human; Rectal disease; Early stage; Malignant tumor; Colonic disease; Abnormal chromosome E18; Rectum; Cytogenetics; Deletion; Digestive diseases; Abnormal chromosome; Genetics; Intestinal disease; Colon; Mutation; Tumor suppressor gene
• ISSN: 0910-5050; 1347-9032; 1349-7006; 1876-4673
• DOI: 10.1111/j.1349-7006.1999.tb00716.x

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.