SEARCH:   Advanced

Blood, 1 January 2009, Vol. 113, No. 1, pp. 100-107. Prepublished online as a Blood First Edition Paper on October 6, 2008; DOI 10.1182/blood-2008-07-166801. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-07-166801v1 113/1/100    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 Sulong, S. Articles by Harrison, C. J. Search for Related Content PubMed PubMed Citation Articles by Sulong, S. Articles by Harrison, C. J. Related Collections Genomics Lymphoid Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  LYMPHOID NEOPLASIA A comprehensive analysis of the CDKN2A gene in childhood acute lymphoblastic leukemia reveals genomic deletion, copy number neutral loss of heterozygosity, and association with specific cytogenetic subgroups Sarina Sulong1, Anthony V. Moorman1,2, Julie A. E. Irving1, Jonathan C. Strefford2,3, Zoe J. Konn2, Marian C. Case1, Lynne Minto1, Kerry E. Barber2, Helen Parker2,3, Sarah L. Wright2, Adam R. M. Stewart2, Simon Bailey4, Nick P. Bown5, Andrew G. Hall1, and Christine J. Harrison1,2 1 Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne; 2 Leukaemia Research Cytogenetics Group and 3 Cancer Genomics Group, Cancer Sciences Division, University of Southampton, Southampton; 4 Royal Victoria Infirmary, Newcastle upon Tyne; and 5 National Health Service (NHS) Northern Genetics Service, Newcastle upon Tyne, United Kingdom Inactivation of the tumor suppressor gene, CDKN2A, can occur by deletion, methylation, or mutation. We assessed the principal mode of inactivation in childhood acute lymphoblastic leukemia (ALL) and frequency in biologically relevant subgroups. Mutation or methylation was rare, whereas genomic deletion occurred in 21% of B-cell precursor ALL and 50% of T-ALL patients. Single nucleotide polymorphism arrays revealed copy number neutral (CNN) loss of heterozygosity (LOH) in 8% of patients. Array-based comparative genomic hybridization demonstrated that the mean size of deletions was 14.8 Mb and biallelic deletions composed a large and small deletion (mean sizes, 23.3 Mb and 1.4 Mb). Among 86 patients, only 2 small deletions were below the resolution of detection by fluorescence in situ hybridization. Patients with high hyperdiploidy, ETV6-RUNX1, or 11q23/MLL rearrangements had low rates of deletion (11%, 15%, 13%), whereas patients with t(9;22), t(1;19), TLX3, or TLX1 rearrangements had higher frequencies (61%, 42%, 78%, and 89%). In conclusion, CDKN2A deletion is a significant secondary abnormality in childhood ALL strongly correlated with phenotype and genotype. The variation in the incidence of CDKN2A deletions by cytogenetic subgroup may explain its inconsistent association with outcome. CNN LOH without apparent CDKN2A inactivation suggests the presence of other relevant genes in this region. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. J. Russell, M. Capasso, I. Vater, T. Akasaka, O. A. Bernard, M. J. Calasanz, T. Chandrasekaran, E. Chapiro, S. Gesk, M. Griffiths, et al. Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia Blood, September 24, 2009; 114(13): 2688 - 2698. [Abstract] [Full Text] [PDF] A. K. Fielding, J. M. Rowe, S. M. Richards, G. Buck, A. V. Moorman, I. J. Durrant, D. I. Marks, A. K. McMillan, M. R. Litzow, H. M. Lazarus, et al. Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemotherapy in the pre-imatinib era: results from the International ALL Trial MRC UKALLXII/ECOG2993 Blood, May 7, 2009; 113(19): 4489 - 4496. [Abstract] [Full Text] [PDF]

	Copyright © 2009 by American Society of Hematology         Online ISSN: 1528-0020