Tavor S, Takeuchi S, Tsukasaki K, Miller C W, Hofmann W K, Ikezoe T, Said J W, Koeffler H P
Division of Hematology/Oncology, Cedars-Sinai Research Institute, UCLA School of Medicine, 8700 Beverly Blvd, D-5068, Los Angeles, CA 90048, USA.
Leuk Lymphoma. 2001 Jul;42(3):517-20. doi: 10.3109/10428190109064610.
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 teleangiecstasia mutated (ATM), modulates the function of p53 and may help mediate cell cycle arrest at G2/M by phosphorylation of Cdc25C. Recently, the human homolog of the checkpoint kinase Cds1 (CHK2) has been suggested to be a tumor suppressor gene. Heterozygous germline mutations have been reported in Li-Fraumeni syndrome (LFS), a highly penetrant familial cancer phenotype, and in sporadic colon cancer. LFS is associated with the development of lymphoid malignancies, especially childhood ALL. Therefore, we analyzed the DNA from 143 lymphoid malignancies to determine whether they had mutations of the CHK2 gene. The 14 exons of CHK2 were studied by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and sequencing of aberrantly migrating bands. One missense mutation changing serine to phenylalanine (codon 428) in an evolutionarily highly conserved domain was found in a non-Hodgkin's aggressive lymphoma. Another point mutation in the non-coding region was identified in one of adult T-cell leukemias (ATL) samples. This result suggests that mutation of the CHK2 gene may rarely be involved in the development of selected lymphomas.
CHK2基因编码一种蛋白激酶，该激酶对于DNA损伤后细胞周期停滞的调节非常重要。CHK2在共济失调毛细血管扩张症突变体（ATM）的下游起作用，调节p53的功能，并可能通过对Cdc25C进行磷酸化来帮助介导G2/M期的细胞周期停滞。最近，检查点激酶Cds1（CHK2）的人类同源物被认为是一种肿瘤抑制基因。在Li-Fraumeni综合征（LFS，一种高度显性的家族性癌症表型）以及散发性结肠癌中，均已报道存在杂合性种系突变。LFS与淋巴恶性肿瘤尤其是儿童急性淋巴细胞白血病（ALL）的发生有关。因此，我们分析了143例淋巴恶性肿瘤的DNA，以确定它们是否存在CHK2基因突变。通过聚合酶链反应-单链构象多态性（PCR-SSCP）以及对异常迁移条带进行测序，对CHK2的14个外显子进行了研究。在一例侵袭性非霍奇金淋巴瘤中，发现了一个错义突变，该突变在一个进化上高度保守的结构域中将丝氨酸变为苯丙氨酸（密码子428）。在一例成人T细胞白血病（ATL）样本中，在非编码区鉴定出另一个点突变。这一结果表明，CHK2基因突变可能很少参与某些淋巴瘤的发生。
