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Blood, 1 February 2008, Vol. 111, No. 3, pp. 1625-1633. Prepublished online as a Blood First Edition Paper on November 15, 2007; DOI 10.1182/blood-2007-08-110130. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2007-08-110130v1 111/3/1625    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sellick, G. S. Articles by Houlston, R. S. Search for Related Content PubMed PubMed Citation Articles by Sellick, G. S. Articles by Houlston, R. S. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Scan of 977 nonsynonymous SNPs in CLL4 trial patients for the identification of genetic variants influencing prognosis Gabrielle S. Sellick1, Rachel Wade2, Susan Richards2, David G. Oscier3, Daniel Catovsky4, and Richard S. Houlston1 1 Section of Cancer Genetics, Institute of Cancer Research, Sutton; 2 Clinical Trial Service Unit, University of Oxford, Oxford; 3 Department of Haematology, Royal Bournemouth Hospital, Bournemouth; 4 Section of Haemato-Oncology, Institute of Cancer Research, Sutton, United Kingdom To identify genetic variants associated with outcome from chronic lymphocytic leukemia (CLL), we genotyped 977 nonsynonymous single nucleotide polymorphisms (nsSNPs) in 755 genes with relevance to cancer biology in 425 patients participating in a phase 3 trial comparing the efficacy of fludarabine, chlorambucil, and fludarabine with cyclophosphamide as first-line treatment. Selection of nsSNPs was biased toward those likely to be functionally deleterious. SNP genotypes were linked to individual patient outcome data and response to chemotherapy. The effect of genotype on progression-free survival (PFS) and overall survival (OS) was assessed by Cox regression analysis adjusting for treatment and clinico-pathologic variables. A total of 78 SNPs (51 dominantly acting and a further 27 recessively acting) were associated with PFS (9 also affecting OS) at the 5% level. These included SNPs mapping to the immune-regulation genes IL16 P434S (P = .03), IL19 S213F (P = .001), LILRA4 P27L (P = .004), KLRC4 S29I (P = .007), and CD5 V471A (P = .002); and DNA response genes POLB P242R (P = .04) and TOPBP1 S730L (P = .02), which were all independently prognostic of immunoglobulin heavy-chain variable region (IgVH) mutational status. The variants identified warrant further evaluation as promising prognostic markers of patient outcome. To facilitate the identification of prognostic markers through pooled analyses, we have made all data from our analysis publicly available. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Moreno-Estrada, K. Tang, M. Sikora, T. Marques-Bonet, F. Casals, A. Navarro, F. Calafell, J. Bertranpetit, M. Stoneking, and E. Bosch Interrogating 11 Fast-Evolving Genes for Signatures of Recent Positive Selection in Worldwide Human Populations Mol. Biol. Evol., October 1, 2009; 26(10): 2285 - 2297. [Abstract] [Full Text] [PDF] A. Enjuanes, Y. Benavente, F. Bosch, I. Martin-Guerrero, D. Colomer, S. Perez-Alvarez, O. Reina, M. T. Ardanaz, P. Jares, A. Garcia-Orad, et al. Genetic Variants in Apoptosis and Immunoregulation-Related Genes Are Associated with Risk of Chronic Lymphocytic Leukemia Cancer Res., December 15, 2008; 68(24): 10178 - 10186. [Abstract] [Full Text] [PDF]

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