Differential rates of frameshift alterations in four repeat sequences of hereditary nonpolyposis colorectal cancer tumors

Autor: A. Couturier, Stylianos E. Antonarakis, Claudine Rey-Berthod, Pierre Hutter, Ariane Paoloni-Giacobino
Rok vydání: 2002
Předmět:
DNA Repair
Base Pair Mismatch
Apoptosis
medicine.disease_cause
Colorectal Neoplasms
Hereditary Nonpolyposis/ genetics
Germline
Amyloid beta-Protein Precursor
Neoplasm Proteins/genetics
Apoptosis/genetics
Receptors
Transforming Growth Factor beta/genetics
Frameshift Mutation
Genetics (clinical)
bcl-2-Associated X Protein
ddc:616
Genetics
Caspase 1
Nuclear Proteins
DNA
Neoplasm
Protein-Serine-Threonine Kinases
Cell Division/genetics
Neoplasm Proteins
Proto-Oncogene Proteins c-bcl-2
Microsatellite
DNA mismatch repair
MutL Protein Homolog 1
Cell Division
Bcl-2-Associated X Protein
Protein Serine-Threonine Kinases
Biology
MLH1
Frameshift mutation
DNA Repair/genetics
Proto-Oncogene Proteins
Base Pair Mismatch/genetics
medicine
Humans
Amyloid beta-Protein Precursor/genetics
DNA
Neoplasm/genetics
Gene
Germ-Line Mutation
Adaptor Proteins
Signal Transducing
Receptor
Transforming Growth Factor-beta Type II
Microsatellite instability
Caspase 1/genetics
medicine.disease
Colorectal Neoplasms
Hereditary Nonpolyposis
Proto-Oncogene Proteins/genetics
Carrier Proteins
Carcinogenesis
Receptors
Transforming Growth Factor beta
Microsatellite Repeats
Zdroj: Human Genetics, Vol. 111, No 3 (2002) pp. 284-289
ISSN: 1432-1203
0340-6717
DOI: 10.1007/s00439-002-0789-0
Popis: DNA sequences of mono-, di-, and trinucleotide repeats are prone to replication errors and thus constitute mutational hot spots. This is well illustrated by the occurrence of DNA microsatellite instability in tumors from patients affected by hereditary nonpolyposis colorectal cancer (HNPCC) resulting from a defect in a gene that participates in postreplicative DNA mismatch repair (MMR). We selected repeat sequences present within coding regions of four genes involved in either cell proliferation or promotion of apoptosis. These repeats consisted of (A)10 in the TGF beta RII, (G)8 in the BAX, (A)8 in the CASP1, and (CCA)7 in the APP genes. These repeats were analyzed in ten tumors from HNPCC patients carrying a germline pathogenic mutation in the MMR gene MLH1. For each tumor the rate of somatic replication errors was measured by sequencing 20-50 cloned PCR-amplified fragments. Substantial intertumor variations were observed in the pattern of repeat alterations, with error rates varying between 12% and 80% for TGF beta RII, 2% and 84% for BAX, 0% and 30% for CASP1, and 0% to 18% for APP. The BAX repeat error rate did not exceed 20% in nine of the ten tumors, in contrast to results from previous studies. High error rates in more than one gene in a same tumor suggested additive selective effects from inactivation of different pathways influencing tumorigenesis. Our methodology can contribute to define tumor characteristics and may, if applied to genes strongly involved in tumorigenesis, improve tumor classification and outcome prediction.
Databáze: OpenAIRE
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