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 eukaryotic cells. They play an important role in the control of the cell cycle. The human CHK2 is a homolog of the yeast G(2) checkpoint kinases known as CDS1 and RAD53. The CHK2 may be a tumor suppressor gene because it was found to be mutated in some individuals with the Li-Fraumeni syndrome. These cases had a normal, non-mutated p53 gene. We performed a mutational analysis of the CHK2 gene using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) in 41 bone marrow samples from individuals with myelodysplastic syndrome (MDS) and 41 samples of acute myeloid leukemias (AML). 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 individual did not have the abnormality. In addition, we demonstrated a previously 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 cycle checkpoint genes in this disease.
Hofmann
W K
WK
Division of Hematology/Oncology, Cedars-Sinai Research Institute, UCLA School of Medicine, 8700 Beverly Boulevard, Suite B213, Los Angeles, CA 90048, USA. w.k.hofmann@em.uni-frankfurt.de
Miller
C W
CW
Tsukasaki
K
K
Tavor
S
S
Ikezoe
T
T
Hoelzer
D
D
Takeuchi
S
S
Koeffler
H P
HP
D000208:Acute Disease; D019943:Amino Acid Substitution; D001853:Bone Marrow / Q000473:pathology; D064447:Checkpoint Kinase 2; D004252:DNA Mutational Analysis; D005260:Female; D018816:Genes, cdc; D006801:Humans; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000209:etiology / Q000235:genetics*; D008297:Male; D009190:Myelodysplastic Syndromes / Q000209:etiology / Q000235:genetics*; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011494:Protein Kinases / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases
D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases