Incidence of chromosomal imbalances in advanced colorectal carcinomas and their metastases.
Comparative genomic hybridization (CGH) was used to screen 54 advanced colon carcinomas. i.e., 24 primary tumors and 30 metastases, for chromosomal alterations. Using a sensitive statistical method for the determination of DNA imbalances and histograms for analysis of the incidence of changes, we identified the DNA over-representation of chromosome 20q as the most common alteration being present in 100% of cases. High incidence deletions were observed on 18q21-18q23 (96%), 4q27-4q28 (96%), 4p14 (87%), 5q21 (81%), 1p21-1p22 (72%), 21q21 (74%), 6q16 (72%), 3p12 (66%), 8p24-8p21 (66%), 9p21 (64%), 11q22 (64%), and 14q13-14q21 (64%). Further frequent over-representation was found on 7q12-7q11.2 (75%), 16p11-16p12 (70%), 19p13 (70%), 9q34 (67%), 19q13 (67%), 13q34 (64%), 13q13 (64%), 17q21 (59%), 22q11 (61%), 8q24 (57%), and 1q21 (57%). Pronounced DNA gains and losses being defined as regions in which the ratio profiles exceeded the values of 1.5 and 0.5, respectively, frequently colocalized with peaks of incidence curve. The use of difference histograms for the comparison of tumor subgroups as well as case-by-case histogram for the analysis of 15 paired tumor samples identified several of the above alterations as relevant for tumor progression and metastasis formation. The study identified additional loci and delineates more precisely those that have been previously reported. For comparative purposes, we have made our primary data (ratio profiles, clinicopathological parameters, histograms) available at the interactive web site http://amba.charite.de/cgh, where the incidence of changes can be determined at individual loci and additional parameters can be applied for the analysis of our CGH results.
Knösel
Thomas
T
Institute of Pathology, University Hospital Charité, Berlin, Germany.
Petersen
Simone
S
Schwabe
Holger
H
Schlüns
Karsten
K
Stein
Ulrike
U
Schlag
Peter Michael
PM
Dietel
Manfred
M
Petersen
Iver
I
D002277:Carcinoma / Q000235:genetics* / Q000556:secondary; D002869:Chromosome Aberrations; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D020732:Cytogenetic Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D017353:Gene Deletion; D005819:Genetic Markers; D006801:Humans; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D009693:Nucleic Acid Hybridization
D004273:DNA, Neoplasm; D005819:Genetic Markers