Counting alleles to predict recurrence of early-stage colorectal cancers Journal Article


Authors: 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.
Article Title: Counting alleles to predict recurrence of early-stage colorectal cancers
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.
Keywords: adult; cancer survival; controlled study; human tissue; aged; disease-free survival; middle aged; survival rate; major clinical study; single nucleotide polymorphism; polymorphism, single nucleotide; disease course; histopathology; cancer staging; follow up; lymph node metastasis; colorectal cancer; allele; metastasis; neoplasm recurrence, local; gene frequency; heterozygote; chromosomes, human, pair 8; prediction; colorectal neoplasms; chromosome aberration; neoplasm metastasis; recurrent disease; chromosome 8p; tumor; technique; genetic markers; chromosome 18q; chromosomes, human, pair 18; allelic imbalance; humans; prognosis; human; male; female; priority journal; article
Journal Title: Lancet
Volume: 359
Issue: 9302
ISSN: 0140-6736
Publisher: Elsevier Science, Inc.  
Date Published: 2002-01-19
Start Page: 219
End Page: 225
Language: English
DOI: 10.1016/s0140-6736(02)07448-2
PUBMED: 11812558
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 14 November 2014 -- Source: Scopus
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  1. Philip B Paty
    496 Paty