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

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....

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Bibliographic Details
Published inInternational journal of cancer Vol. 53; no. 3; p. 382
Main Authors Ookawa, K, Sakamoto, M, Hirohashi, S, Yoshida, Y, Sugimura, T, Terada, M, Yokota, J
Format Journal Article
LanguageEnglish
Published United States 01.02.1993
Subjects
Alleles
Chromosomes, Human, Pair 13
Chromosomes, Human, Pair 14
Colorectal Neoplasms - genetics
Colorectal Neoplasms - pathology
DNA, Neoplasm - genetics
Genes, DCC
Genes, p53
Humans
Liver Neoplasms - genetics
Liver Neoplasms - secondary
Polymorphism, Restriction Fragment Length
Sequence Deletion
Tumor Suppressor Protein p53 - genetics
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Summary: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.
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.2910530307