Concordant p53 and DCC alterations and allelic losses on chromosomes 13q and 14q associated with liver metastases of colorectal carcinoma

Abstract

To identify genetic alterations associated with acquisition of metastatic ability in colorectal carcinoma, 31 liver metastases and 40 primary tumors of colorectal carcinoma from 55 patients were analyzed for loss of chromosomal heterozygosity using 46 polymorphic DNA markers covering 15 chromosomes. Loss of heterozygosity (LOH) and/or rearrangement at the TP53 and DCC loci were detected in all liver metastases (10 of 10 at TP53 and 19 of 19 at DCC), and were observed in 59% (10 of 17) at TP53 and 75% (18 of 24) at DCC respectively in the primary tumors. Furthermore, the incidence of LOH on chromosomes 13q and 14q was higher than that on other chromosomes in liver metastasis, and it was higher in liver metastases than in primary tumors (20/30 vs. 18/39, p = 0.072 on chromosome 13q and 21/31 vs. 16/40, p = 0.018 on chromosome 14q). In 4 cases, LOH or rearrangement at loci on chromosomes 13q, 14q and 18q not detected in primary tumors was observed in liver metastases from the same patients. These results suggest that concordant p53 and DCC alterations and inactivation of several other tumor-suppressor genes, especially those on chromosomes 13q and 14q, play important roles in the acquisition of metastatic potential of colorectal carcinoma.

Suppression of invasive properties of colon cancer cells by a metastasis suppressor KAI1 gene

“…Recent con¯icting results, however, have revealed no signi®cant relationship between Nm23 expression and metastatic ability of colon cancer cells (Haut et al, 1988;Cohn et al, 1991;Myero and Markowitz, 1993;Wang et al, 1993;Whitelaw and Northover, 1993). DCC also seemed to be a candidate tumor suppressor gene, deletions and somatic mutation of which have been observed in a number of colorectal cancers (Fearon et al, 1990;Ookawa et al, 1993). Our previous report showed some relationship between colon cancer DCC mRNA expression and the presence of liver metastasis (Itoh et al, 1993).…”

Frequent reduction or loss of DCC gene expression in human osteosarcoma

“…Moreover, it has been suggested that DCC may act as a metastatic suppressor in colon carcinoma (Ookawa et al, 1993 Reale et al, 1994 (Fearon et al, 1990). …”

Tumour heterogeneity and clonality – an old theme revisited

“…Tumour subclones bearing a particular marker may be missed in the specimen selected for analysis and yet they may behave differently from tumour tissue represented in the biopsy analysed [39,45]. Accordingly, metastatic foci of such cancers, for example in the liver, may harbour molecular abnormalities that are not readily detectable throughout the corresponding primary tumours [46].…”