Evidence for various 20q status using allelotyping, CGH arrays, and quantitative PCR in distal CIN colon cancers.
The genomic aberration profile of chromosome 20q in distal CIN colon carcinomas was analysed using allelotyping and CGH arrays. Allelotyping revealed carcinomas with allelic imbalance along the full long arm, and carcinomas with fully non-aberrant 20q. Oligonucleotide-based CGH showed that among the carcinomas without allelic imbalance, 47% had in fact a gain. In this subgroup, quantitative PCR for the TOPI gene (20q12) confirmed this gain, and fluorescence in situ hybridization showed that the chromosome 20q gain resulted from tetra/polysomy instead of aneusomy. The 20q gain correlated with a high frequency of aberrations, with allelic imbalance at TP53 locus but not at APC locus, and carcinomas with a disomic 20q showed low frequency of genomic aberrations and were significantly associated to mucinous phenotype. The prognostic value of 20q amplification was not demonstrated in this study. These results indicate that on the basis of aberration frequency, chromosome 20q and TP53/APC locus status, distal CIN carcinomas harbor a high degree of genetic heterogeneity suggesting several pathways for carcinogenesis. This study also indicates that allelotyping needs to be carried out with a complementary technique, such as quantitative PCR.
Nicolet
Céline
C
Inserm, U682, 3 Avenue Motière Strasbourg, F-67200 France.
Guérin
Eric
E
Neuville
Agnès
A
Kerckaert
Jean-Pierre
JP
Wicker
Nicolas
N
Bergmann
Etienne
E
Brigand
Cécile
C
Kedinger
Michèle
M
Gaub
Marie-Pierre
MP
Guenot
Dominique
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D043171:Chromosomal Instability; D002890:Chromosomes, Human, Pair 20; D003110:Colonic Neoplasms / Q000235:genetics*; D055028:Comparative Genomic Hybridization / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods*