Alterations of the DPC4 Gene in Human Colorectal Cancers

Chang, Sae Kyuong; Moon, Cheol; Kim, Jeong Wook; Heo, Cheol Heang; Yoo, Kyung Kum; Kim, Hyung Jun; Do, Jae Hyuk; Joe, Jun Hyung

Abstract

Baekground/Aims: Tumor suppressor genes are characterized by inactivation of both alleles, that is, especially loss of heterozygosity (LOH). The LOH at 18q21 chromosome region has been reported to be frequent in pancreatic and colon cancer. The chromosome region 18q21 has been shown to be frequently deleted in colorectal cancer. Such frequent allelic loss indicates the presence of a tumor suppressor gene in colorectal cancer. The DPC4 gene, which is located at the 18q21, has been identified as a putative tumor suppressor gene he from the studies of pancreatic cancer. The aim of the present study was to determine whether it is also altered in colorectal cancer.
METHODS
For 30 colorectal cancer tissues, we performed PCR-single strand conformation polymarphism (SSCP) with modified 'cold SSCP and silver sequencing.
RESULTS
The DPC4 gene mutation of coIorectal cancer was found in 9 out of the 30 specimens (30%). Among the 9 specimens, mutations of exon 1, 8, and 10 were observed in 2 of 9 (22%), in 6 of 9 (66%) and in 1 of 9 (11%), respectively. Silver sequence showed substitution in 4 cases (44%), insertion in 4 cases (44%), silent mutation in 1 case (12%) and deletion was not observed. Presence of DPC4 mutation was correlated with tumor differentiation (well or moderate vs. poorly differentiation; p<0.05).
CONCLUSIONS
The DPC4 gene may be related to tumor development in a fraction of colorectal cancers.