Cytogenetics of colorectal adenocarcinomas.
The occurrence of nonrandom chromosomal anomalies in colorectal adenocarcinomas could be demonstrated from the cytogenetic study of 100 cases. The most frequent changes are a rearrangement of chromosome 17, leading to the loss of its short arm and a loss of one chromosome 18. Three types of tumors with abnormal karyotypes can be defined. First are the monosomic-type near-diploid tumors (MD), characterized by a monosomy of both 17p and chromosome 18 mostly associated with other recurrent monosomies. In two of three cases, one or several minor derived polyploid subclones are also observed. Second are the monosomic-type polyploid tumors (MP), which have a pattern of chromosome imbalance very similar to that of MD tumors. They derive from MD tumors by endoreduplication followed by complete disappearance of the original MD clone. Third are the trisomic-type tumors (TT), which lose either 17p or chromosome 18 or none, most of the anomalies being gains of entire chromosomes. These TT tumors never undergo endoreduplication. In addition, seven tumors with normal karyotypes were found and may constitute another category (NT). A nonrandom distribution of these tumor types in relation to tumor site was observed, since in the distal colon, TT and NT tumors are underrepresented and endoreduplications are significantly more frequent. The level of chromosomal mutagenesis is two- to threefold higher in MD and MP than in TT tumors. More than 95% of the rearrangements are unbalanced, and most of them result from breakpoints located in juxtacentromeric heterochromatin. A good correlation is found between our results and the available molecular data on allelic losses. The involvement of recessive tumor suppressor genes in colorectal tumorigenesis and the possible relationship between chromosomal imbalances and deviations in metabolic pathways is described.
Muleris
M
M
Department of Biology, Institut Curie, Paris, France.
Salmon
R J
RJ
Dutrillaux
B
B
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D011003:Ploidies
D005819:Genetic Markers