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Blood, 1 February 2007, Vol. 109, No. 3, pp. 916-925. Prepublished online as a Blood First Edition Paper on October 17, 2006; DOI 10.1182/blood-2006-03-011825. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-03-011825v1 109/3/916    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 Ng, D. Articles by Toro, J. R. Search for Related Content PubMed PubMed Citation Articles by Ng, D. Articles by Toro, J. R. Related Collections Clinical Trials and Observations Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Identification of a novel chromosome region, 13q21.33-q22.2, for susceptibility genes in familial chronic lymphocytic leukemia David Ng1, Ousmane Toure1, Ming-Hui Wei1,2, Diane C. Arthur3, Fatima Abbasi4, Laura Fontaine5, Gerald E. Marti4, Joseph F. Fraumeni, Jr6, Lynn R. Goldin1, Neil Caporaso1, and Jorge R. Toro1 1 Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Rockville, MD; 2 Program of Division of Cancer Epidemiology and Genetics, Science Applications International Corporation (SAIC)–Frederick, Frederick, MD; 3 Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, NIH, DHHS, Bethesda, MD; 4 Flow and Image Cytometry Laboratory, Cellular Therapy and Tissues Branch, Division of Gene and Cell Therapy, Food and Drug Administration/Center for Biologics Evaluation and Research, Bethesda, MD; 5 Westat, Rockville, MD; 6 Office of the Director, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Rockville, MD Chronic lymphocytic leukemia (CLL) is the most prevalent form of leukemia in adults in western countries. A genome scan of CLL-prone families revealed a lod score of one in band 13q22.1. To investigate this finding, we selected 6 CLL families consisting of 63 individuals (CLL affected, n = 19; unaffected, n = 44) for fine mapping of a 23-megabase region in 13q14.2-q22.2. Interphase fluorescence in situ hybridization (FISH) revealed 13q14 deletion in 85% (11/13) of CLL patients. Four CLL families shared a 3.68-Mb minimal region in 13q21.33-q22.2. Two asymptomatic siblings who shared the 13q21.33-q22.2 at-risk haplotype exhibited CD5+ monoclonal B-cell lymphocytosis (MBL) on flow cytometry. One of these individuals also had a 13q14 deletion by FISH. These 2 individuals with MBL shared the at-risk haplotype with their CLL-affected relatives, providing further evidence of the relationship between CLL and MBL, as well as of the biologic significance of this novel region. Using direct DNA sequencing analysis, we screened 13 genes for mutations, but no frameshift or nonsense mutations were detected. Our studies revealed that 11 of the 13 genes in the candidate region were expressed in immune tissues, supporting their functional relevance in investigations of familial CLL. In conclusion, we identified a novel candidate region that may predispose to familial CLL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. W. Hauswirth and U. Jager Impact of cytogenetic and molecular prognostic markers on the clinical management of chronic lymphocytic leukemia Haematologica, January 1, 2008; 93(1): 14 - 19. [Full Text] [PDF] E. S. Raveche, E. Salerno, B. J. Scaglione, V. Manohar, F. Abbasi, Y.-C. Lin, T. Fredrickson, P. Landgraf, S. Ramachandra, K. Huppi, et al. Abnormal microRNA-16 locus with synteny to human 13q14 linked to CLL in NZB mice Blood, June 15, 2007; 109(12): 5079 - 5086. [Abstract] [Full Text] [PDF] L. R. Goldin and S. L. Slager Familial CLL: Genes and Environment Hematology, January 1, 2007; 2007(1): 339 - 345. [Abstract] [Full Text] [PDF]

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