Analysis of the CHK2 gene in lymphoid malignancies

The CHK2 gene encodes a protein kinase that is important for the regulation of cell cycle arrest after DNA damage. CHK2 acts downstream of ataxia tele angiecstasia mutated (ATM), modulates the function of p53 and may help medi ate cell cycle arrest at G2/M by phosphorylation of Cdc25C. Recently, the h uman homolog of the checkpoint kinase Cds I (CHK2) has been suggested to be a tumor suppressor gene. Heterozygous germline mutations have been reporte d in Li-Fraumeni syndrome (LFS), a highly penetrant familial cancer phenoty pe, and in sporadic colon cancer. LFS is associated with the development of lymphoid malignancies, especially childhood ALL. Therefore, we analyzed th e DNA from 143 lymphoid malignancies to determine whether they had mutation s of the CHK2 gene. The 14 exons of CHK2 were studied by polymerase chain r eaction-single strand conformational polymorphism (PCR-SSCP) and sequencing of aberrantly migrating bands. One missense mutation changing serine to ph enylalanine (codon 428) in an evolutionarily highly conserved domain was fo und in a non-Hodgkin's aggressive lymphoma. Another point mutation in the n on-coding region was identified in one of adult T-cell leukemias (ATL) samp les. This result suggests that mutation of the CHK2 gene may rarely be invo lved in the development of selected lymphomas.