The relationship of DNA aneuploidy to molecular genetic alterations in colorectal carcinoma

G. Johan A Offerhaus, Eimert P. De Feyter, Cornelis J. Cornelisse, Kasper W F Tersmette, Jeffrey Floyd, Scott E Kern, Bert Vogelstein, Stanley R. Hamilton

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1612-1619
Number of pages8
JournalGastroenterology
Volume102
Issue number5
StatePublished - 1992

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Aneuploidy
Molecular Biology
Colorectal Neoplasms
Loss of Heterozygosity
DNA
Carcinoma
Neoplasms
Diploidy
Flow Cytometry
Neoplasm Metastasis
ras Genes
Ploidies
Survival Analysis
Chromosomes
Mutation
Survival

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Offerhaus, G. J. A., De Feyter, E. P., Cornelisse, C. J., Tersmette, K. W. F., Floyd, J., Kern, S. E., ... Hamilton, S. R. (1992). The relationship of DNA aneuploidy to molecular genetic alterations in colorectal carcinoma. Gastroenterology, 102(5), 1612-1619.

The relationship of DNA aneuploidy to molecular genetic alterations in colorectal carcinoma. / Offerhaus, G. Johan A; De Feyter, Eimert P.; Cornelisse, Cornelis J.; Tersmette, Kasper W F; Floyd, Jeffrey; Kern, Scott E; Vogelstein, Bert; Hamilton, Stanley R.

In: Gastroenterology, Vol. 102, No. 5, 1992, p. 1612-1619.

Research output: Contribution to journalArticle

Offerhaus, GJA, De Feyter, EP, Cornelisse, CJ, Tersmette, KWF, Floyd, J, Kern, SE, Vogelstein, B & Hamilton, SR 1992, 'The relationship of DNA aneuploidy to molecular genetic alterations in colorectal carcinoma', Gastroenterology, vol. 102, no. 5, pp. 1612-1619.
Offerhaus GJA, De Feyter EP, Cornelisse CJ, Tersmette KWF, Floyd J, Kern SE et al. The relationship of DNA aneuploidy to molecular genetic alterations in colorectal carcinoma. Gastroenterology. 1992;102(5):1612-1619.
Offerhaus, G. Johan A ; De Feyter, Eimert P. ; Cornelisse, Cornelis J. ; Tersmette, Kasper W F ; Floyd, Jeffrey ; Kern, Scott E ; Vogelstein, Bert ; Hamilton, Stanley R. / The relationship of DNA aneuploidy to molecular genetic alterations in colorectal carcinoma. In: Gastroenterology. 1992 ; Vol. 102, No. 5. pp. 1612-1619.
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abstract = "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.",
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T1 - The relationship of DNA aneuploidy to molecular genetic alterations in colorectal carcinoma

AU - Offerhaus, G. Johan A

AU - De Feyter, Eimert P.

AU - Cornelisse, Cornelis J.

AU - Tersmette, Kasper W F

AU - Floyd, Jeffrey

AU - Kern, Scott E

AU - Vogelstein, Bert

AU - Hamilton, Stanley R.

PY - 1992

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N2 - 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.

AB - 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.

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