The relationship of DNA aneuploidy to molecular genetic alterations in colorectal carcinoma.
Altered total nuclear DNA content is frequent in colorectal carcinomas, but the mechanisms producing aneuploidy are unknown. Therefore, DNA ploidy by flow cytometry was correlated with molecular genetic alterations and tumor characteristics in 50 colorectal carcinomas. The prognostic value of these alterations was also evaluated because aneuploidy has been associated with poor prognosis. Thirty-nine of the carcinomas (78%) were DNA aneuploid. When compared with diploid carcinomas, aneuploid tumors had greater mean fractional allelic loss, defined as the fraction of evaluable nonacrocentric autosomal arms with deletion (0.25 +/- 0.15, range 0-0.667, vs. 0.12 +/- 0.10, range 0-0.345; P = 0.006). DNA index by flow cytometry correlated with fractional allelic loss (r = 0.38, P = 0.006). Aneuploid tumors also had more frequent allelic loss on chromosome 17p (87% vs. 55%; P = 0.017), but less frequent ras gene mutation (44% vs. 82%; P = 0.025). Among the 25 right-sided and 25 left-sided tumors, DNA diploid tumors were more frequent on the right side (P = 0.002), whereas deletion of 17p was found predominantly on the left side. Aneuploidy was associated with moderate and poor differentiation of the carcinomas but not with distant metastasis. By contrast, high fractional allelic loss, deletion of 17p, and deletion of 18q were associated with distant metastasis. In survival analysis of patients with Dukes' B or C carcinoma, DNA aneuploidy was not a significant discriminator, but patients whose tumor had deletion of 17p or deletion of both 17p and 18q had poorer survival (P = 0.045 and 0.022, respectively). The results suggest that DNA aneuploidy is associated with some of the molecular genetic alterations and phenotypic characteristics of colorectal carcinomas but is not a reliable indicator of metastatic potential.
Offerhaus
G J
GJ
Department of Pathology, Johns Hopkins University School of Medicine and Hospital, Baltimore, Maryland.
De Feyter
E P
EP
Cornelisse
C J
CJ
Tersmette
K W
KW
Floyd
J
J
Kern
S E
SE
Vogelstein
B
B
Hamilton
S R
SR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D011905:Genes, ras; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D015996:Survival Rate
D004273:DNA, Neoplasm