1. ¹Laboratory of Pathology, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
2. ²The Cancer Epigenetics Laboratory, Molecular Pathology Program, Spanish National Cancer Center (CNIO), Madrid, Spain
3. ³Institute of Pathology, University of Würzburg, Würzburg, Germany

Correspondence: Dr E Campo, Laboratory of Pathology, Hospital Clinic, Villarroel 170, 08036 Barcelona, Spain. Fax: +34 93 2275717; E-mail: ecampo@clinic.ub.es

Received 26 March 2004; Accepted 22 September 2004; Published online 4 November 2004.

Abstract

CHK1 gene encodes for a serine/threonine kinase involved in the regulation of cell cycle progression and DNA damage checkpoints. To determine the role of CHK1 in the pathogenesis of lymphoid neoplasms and its relationship to other DNA damage response genes, we have analyzed the gene status, protein, and mRNA expression in a series of tumors and nonneoplastic lymphoid tissues. CHK1 protein and mRNA expression levels were very low in both reactive tissues and resting lymphoid cells, whereas tumor samples showed a variable pattern of expression related to their proliferative activity. However, seven aggressive tumors showed a dissociate pattern of extremely low or negative protein expression in spite of a high proliferative activity. Four of these tumors were diffuse large B-cell lymphomas (DLCLs) with concordant reduced levels of mRNA, whereas one blastoid mantle cell lymphoma (B-MCL) and two DLCLs had relatively normal levels of mRNA. No gene mutations, deletions, or hypermethylation of the promoter region were detected in any of these cases. In all these tumors ATM, CHK2, and p53 genes were wild type. These findings suggest that CHK1 inactivation in NHLs occurs by loss of protein expression in a subset of aggressive variants alternatively to ATM, CHK2, and p53 alterations.