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Prepublished online as a Blood First Edition Paper on August 1, 2002; DOI 10.1182/blood-2002-04-1078. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-04-1078v1 100/13/4602    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 Tort, F. Articles by Campo, E. Search for Related Content PubMed PubMed Citation Articles by Tort, F. Articles by Campo, E. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 December 2002, Vol. 100, No. 13, pp. 4602-4608 NEOPLASIA CHK2-decreased protein expression and infrequent genetic alterations mainly occur in aggressive types of non-Hodgkin lymphomas Frederic Tort, Silvia Hernàndez, Silvia Beà, Antonio Martínez, Manel Esteller, James G. Herman, Xavier Puig, Emma Camacho, Montse Sánchez, Iracema Nayach, Armando Lopez-Guillermo, Pedro L. Fernández, Dolors Colomer, Luis Hernàndez, and Elias Campo From the Laboratory of Pathology, Hospital Clinic, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), University of Barcelona; the Information and Studies Service, Department of Health and Social Security; and the Department of Haematology, Hospital Clinic, Barcelona, Spain; the Cancer Epigenetics Laboratory, Molecular Pathology Program, Spanish National Cancer Research Center (CNIO), Madrid, Spain; and The Johns Hopkins Oncology Center, Baltimore, MD. The CHK2 gene codifies for a serine/threonine kinase that plays a central role in DNA damage response pathways. To determine the potential role of CHK2 alterations in the pathogenesis of lymphoid neoplasms we have examined the gene status, protein, and mRNA expression in a series of tumors and nonneoplastic lymphoid samples. A heterozygous Ile157Thr substitution, also present in the germ line of the patient, was detected in a blastoid mantle cell lymphoma (MCL). CHK2 protein and mRNA expression levels were similar in all types of lymphomas and reactive samples, and these levels were independent of the proliferative activity of the tumors. However, 5 tumors, one typical MCL, 2 blastoid MCLs, and 2 large cell lymphomas, showed marked loss of protein expression, including 2 samples with complete absence of CHK2 protein. These 2 lymphomas showed the highest number of chromosomal imbalances detected by comparative genomic hybridization in the whole series of cases. However, no mutations, deletions, or hypermethylation of the promoter region were identified in any of these tumors. mRNA levels were similar in cases with low and normal protein expression, suggesting a posttranscriptional regulation of the protein in these tumors. CHK2 gene and protein alterations were not related to p53 and ATM gene status. In conclusion, CHK2 alterations are uncommon in malignant lymphomas but occur in a subset of aggressive tumors independently of p53 or ATM alterations. The high number of chromosomal imbalances in tumors with complete absence of CHK2 protein suggests a role of this gene in chromosomal instability in human lymphomas. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Reimann, C. Loddenkemper, C. Rudolph, I. Schildhauer, B. Teichmann, H. Stein, B. Schlegelberger, B. Dorken, and C. A. Schmitt The Myc-evoked DNA damage response accounts for treatment resistance in primary lymphomas in vivo Blood, October 15, 2007; 110(8): 2996 - 3004. [Abstract] [Full Text] [PDF] E. M. Kass, J. Ahn, T. Tanaka, W. A. Freed-Pastor, S. Keezer, and C. Prives Stability of Checkpoint Kinase 2 Is Regulated via Phosphorylation at Serine 456 J. Biol. 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