Mutation analysis of the DNA-damage checkpoint gene CHK2 in myelodysplastic syndromes and acute myeloid leukemias

Checkpoint genes code for a family of proteins which sense DNA damage in eu karyotic cells. They play an important role in the control of the cell cycl e. The human CHK2 is a homolog of the yeast G(2) checkpoint kinases known a s CDS1 and RAD53. The CHK2 may be a tumor suppressor gene because it was fo und to be mutated in some individuals with the Li-Fraumeni syndrome. These cases had a normal, non-mutated p53 gene. We performed a mutational analysi s of the CHK2 gene using polymerase chain reaction-single strand conformati on polymorphism (PCR-SSCP) in 41 bone marrow samples from individuals with myelodysplastic syndrome (MDS) and 41 samples of acute myeloid leukemias (A ML). We found a novel G to C transversion resulting in a change from Ala to Gly at codon 507 of CHK2 in one MDS sample, but normal cells from this ind ividual did not have the abnormality. In addition, we demonstrated a previo usly described polymorphism at codon 84 (A to G at nucleotide 252) of exon 1 of CHK2 in three of 41 MDS and three of 41 AML patients. The presence of a CHK2 mutation in MDS highlights the importance of alterations of cell cyc le checkpoint genes in this disease. (C) 2001 Elsevier Science Ltd. All rig hts reserved.