CHK2-decreased protein expression and infrequent genetic alterations mainly occur in aggressive types of non-Hodgkin lymphomas

Autor: Silvia Hernández, Luis Hernández, Dolors Colomer, Antonio Martinez, James G. Herman, Armando López-Guillermo, Manel Esteller, Sílvia Beà, Elias Campo, Frederic Tort, Xavier Puig, M. Sánchez, Pedro Luis Sánchez Fernández, Emma Camacho, Iracema Nayach
Rok vydání: 2002
Předmět:
Pathology
medicine.medical_specialty
Lymphoid Tissue
Immunology
Mutation
Missense
Cell Cycle Proteins
Ataxia Telangiectasia Mutated Proteins
Lymphoma
Mantle-Cell
Protein Serine-Threonine Kinases
medicine.disease_cause
Blastoid
Biochemistry
Chromosome instability
medicine
Humans
RNA
Messenger
RNA
Neoplasm
Gene
Polymorphism
Single-Stranded Conformational
Chromosome Aberrations
Mutation
biology
Reverse Transcriptase Polymerase Chain Reaction
Lymphoma
Non-Hodgkin
Tumor Suppressor Proteins
Cell Biology
Hematology
DNA Methylation
medicine.disease
biology.organism_classification
Genes
p53
Leukemia
Lymphocytic
Chronic
B-Cell
Lymphoma
Neoplasm Proteins
DNA-Binding Proteins
Gene Expression Regulation
Neoplastic
Checkpoint Kinase 2
Ki-67 Antigen
Amino Acid Substitution
Enzyme Induction
DNA methylation
Cancer research
Mantle cell lymphoma
Lymphoma
Large B-Cell
Diffuse
Protein Kinases
Cell Division
Gene Deletion
Comparative genomic hybridization
Zdroj: Blood. 100(13)
ISSN: 0006-4971
Popis: 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 ATMgene 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.
Databáze: OpenAIRE
Externí odkaz: