Genetic alterations within the retinoblastoma locus in colorectal carcinomas. Relation to DNA ploidy pattern studied by flow cytometric analysis.
Alterations within the retinoblastoma (Rb) gene, as detected by the VNTR probe p68RS2.0, and flow cytometric DNA pattern have been analysed in 255 colorectal carcinomas. A total of 35.3% of the tumours had alterations within the Rb gene. Amplification of one allele was demonstrated in 29.5% of the tumours, and loss of heterozygosity was found in 11.5%. No association was found between amplification within the Rb gene and clinicopathological characteristics of the patients. The high frequency of alterations demonstrated within the Rb gene, suggests that this gene is involved in colorectal carcinogenesis with amplification as by far the most abundant genetic alteration. This may imply that the Rb gene has an oncogene-like function in colorectal carcinomas, rather than acting as a tumour suppressor gene. Sixty-three per cent of the carcinomas were DNA aneuploid, and a significant association was demonstrated between amplification within the Rb gene and DNA aneuploidy (P less than 0.01). Two other chromosome loci were analysed, on chromosome 1p (probe pYNZ2) and on chromosome 2p (probe pYNH24), respectively. On chromosome 1p, heterozygous loss was found in 22.2% of the tumours, indicating an involvement of this chromosome in a subset of colorectal carcinomas.
Meling
G I
GI
Institute of Forensic Medicine, National Hospital, University of Oslo, Norway.
Lothe
R A
RA
Børresen
A L
AL
Hauge
S
S
Graue
C
C
Clausen
O P
OP
Rognum
T O
TO
D000483:Alleles; D015139:Blotting, Southern; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D015342:DNA Probes; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D016161:Genes, Retinoblastoma; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D011003:Ploidies; D012004:Rectal Neoplasms / Q000235:genetics*; D015183:Restriction Mapping
D015342:DNA Probes; D004273:DNA, Neoplasm