Nakao M, Yokota S, Kaneko H, Seriu T, Koizumi S, Takaue Y, Fujimoto T, Misawa S
Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
Leukemia. 1996 Feb;10(2):249-54.
We analyzed homozygous deletions and mutations of the CDKN2(p16(INK4A)/MTS1) gene, using polymerase chain reaction and Southern blot analysis, in 120 children with acute lymphoblastic leukemia (ALL). Homozygous deletion was found in 17 of 89 (19%) precursor B-ALL patients, in 11 of 24 (46%) T-ALL patients, and in 0 of 7 other phenotype ALL patients. After excluding 28 (23%) patients who showed a homozygous deletion of CDKN2, we found that three patients (3%) had mutation at exon 2 of CDKN2 using PCR-SSCP and sequencing strategy. One had a CGA to TGA nonsense mutation (Arg to stop) at codon 72, one had a 1-bp deletion at codon 117, and the third had a 2-bp deletion at codon 70, resulting in frameshifts in the two latter patients. All three of these patients were T phenotype ALL, and the incidence of mutation in the 24 T-ALL patients examined was 13%. In contrast, no mutation was detected in the remaining patients with precursor-B or other type ALL (0/96). Our results suggest that mutational inactivation of the CDKN2 gene may contribute to the leukemogenic growth, especially in some patients with T-ALL.
我们采用聚合酶链反应和Southern印迹分析技术，对120例急性淋巴细胞白血病（ALL）患儿的CDKN2（p16(INK4A)/MTS1）基因纯合缺失和突变情况进行了分析。在89例前体B-ALL患者中有17例（19%）发现纯合缺失，24例T-ALL患者中有11例（46%）发现纯合缺失，7例其他表型ALL患者中未发现纯合缺失。在排除28例（23%）显示CDKN2纯合缺失的患者后，我们采用PCR-SSCP和测序策略发现3例患者（3%）的CDKN2第2外显子存在突变。1例在密码子72处发生CGA到TGA的无义突变（从精氨酸变为终止密码子），1例在密码子117处发生1个碱基缺失，第3例在密码子70处发生2个碱基缺失，后两例患者发生移码突变。这3例患者均为T表型ALL，在所检测的24例T-ALL患者中突变发生率为13%。相比之下，其余前体B型或其他类型ALL患者未检测到突变（0/96）。我们的结果表明，CDKN2基因的突变失活可能有助于白血病的生长，尤其是在一些T-ALL患者中。
