Counting alleles to predict recurrence of early-stage colorectal cancers

Wei Zhou, Steven N. Goodman, Gennaro Galizia, Eva Lieto, Francesca Ferraraccio, Carlo Pignatelli, Colin A. Purdie, Juan Piris, Robert Morris, David J. Harrison, Philip B. Paty, Al Culliford, Katharine E. Romans, Elizabeth A. Montgomery, Michael A. Choti, Kenneth W. Kinzler, Bert Vogelstein

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Abstract

Background: Chromosome imbalances occur in many cancers and represent important biological properties of tumours. However, measurements of such imbalances are difficult. We used a new, quantitative approach to investigate the prognostic value of chromosome imbalances in early-stage colorectal cancers. Methods: We studied 180 patients with no evidence of lymph-node or distant metastases at the time of surgery. DNA from paraffin-embedded tumours was tested for imbalances of chromosome 8p and 18q by digital SNP (single-nucleotide polymorphism) - a technique in which each allele in a sample is directly counted. Surviving patients had median follow-up of 68 months, and disease recurrence was used as the clinical endpoint. Findings: Tumours were divided into three groups: "L" tumours (n = 93) had allelic imbalances of chromosomes 8p and 18q, "L/R" tumours (n = 60) had allelic imbalances of either chromosome 8p or 18q but not both, and "R" tumours (n = 27) retained allelic balance for both chromosomes. 5-year disease-free survival was 100% (95% CI 80-100) for patients with R tumours, 74% (61-87) for patients with L/R tumours, and 58% (47-69) for those with L tumours. These differences were significant (p < 0.0001) and were independent of other variables - eg, Duke's stage A tumours of class L were much more likely to recur than Duke's stage B tumours of class R (p = 0.002). Interpretation: In patients without metastasis, allelic imbalance is a better predictor of prognosis than histopathological stage.

Original languageEnglish (US)
Pages (from-to)219-225
Number of pages7
JournalLancet
Volume359
Issue number9302
DOIs
StatePublished - Jan 19 2002

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ASJC Scopus subject areas

  • Medicine(all)

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Zhou, W., Goodman, S. N., Galizia, G., Lieto, E., Ferraraccio, F., Pignatelli, C., Purdie, C. A., Piris, J., Morris, R., Harrison, D. J., Paty, P. B., Culliford, A., Romans, K. E., Montgomery, E. A., Choti, M. A., Kinzler, K. W., & Vogelstein, B. (2002). Counting alleles to predict recurrence of early-stage colorectal cancers. Lancet, 359(9302), 219-225. https://doi.org/10.1016/S0140-6736(02)07448-2