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PMID: 9342373 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Alternative genetic pathways in colorectal carcinogenesis.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 94 ·No. 22 ·1997-10-28 ·Pages 12122-7

Olschwang S, Hamelin R, Laurent-Puig P, Thuille B, De Rycke Y, Li YJ, Muzeau F, Girodet J, Salmon RJ, Thomas G

Abstract

The comparative typing of matched tumor and blood DNAs at dinucleotide repeat (microsatellite) loci has revealed in tumor DNA the presence of alleles that are not observed in normal DNA. The occurrence of these additional alleles is possibly due to replication errors (RERs). Although this observation has led to the recognition of a subtype of colorectal cancer with a high incidence of RERs (caused by a deficiency in DNA mismatch repair), a thorough analysis of the RER frequency in a consecutive series of colorectal cancers had not been reported. It is shown here that the extensive typing of 88 colorectal tumors reveals a bimodal distribution for the frequency of RER at microsatellite loci. Within the major mode (75 tumors, RER- subtype), the probability that a locus exhibited instability did not differ significantly among loci and tumors, being 0.02. The subsequent development of a statistical test for an operational discrimination between the RER- and RER+ subtypes indicated that the probability of misclassification did not exceed 0.001 in this series. The frequency of K-ras mutation was found to be equivalent in the two subtypes. However, in the RER+ tumors, the p53 gene mutation was less frequently detected, the adenomatous polyposis coli (APC) mutation was rare, and the biallelic inactivation of either of these genes was not observed. Furthermore, the concomitant occurrence of APC and tumor growth factor beta receptor type II gene alterations was found only once. These data suggest that the repertoires of genes that are frequently altered in RER+ and RER- tumors may be more different than previously thought.

MeSH Terms
Aged Chi-Square Distribution Chromosome Deletion Chromosomes, Human, Pair 17 Chromosomes, Human, Pair 5 Colorectal Neoplasms/classification,etiology,genetics DNA Replication/genetics DNA, Neoplasm/classification,genetics Dinucleotide Repeats Genes, APC Genes, p53 Genes, ras Genotype Humans Middle Aged Mutagenesis Point Mutation Protein Serine-Threonine Kinases Receptor, Transforming Growth Factor-beta Type II Receptors, Transforming Growth Factor beta/genetics
Chemicals
DNA, Neoplasm Receptors, Transforming Growth Factor beta Protein Serine-Threonine Kinases Receptor, Transforming Growth Factor-beta Type II
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Olschwang S
Institut National de la Santé et de la Recherche Médicale U434, Centre d'Etude du Polymorphisme Humain, 27 rue Juliette Dodu, 75010 Paris, France.
Hamelin R
Laurent-Puig P
Thuille B
De Rycke Y
Li Y J
Muzeau F
Girodet J
Salmon R J
Thomas G
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.94.22.12122
Published
1997-10-28
Pages
12122-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC23723
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.94.22.12122 PMC Full Text View journal details
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