Bullrich F, Rasio D, Kitada S, Starostik P, Kipps T, Keating M, Albitar M, Reed J C, Croce C M
Kimmel Cancer Institute and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Cancer Res. 1999 Jan 1;59(1):24-7.
Mutations in the ATM gene located on the long arm of chromosome 11 at 11q22-23 cause ataxia-telangiectasia, an autosomal recessive disorder that is associated with increased incidence of malignancy and, particularly, lymphoid tumors. A role for ATM in the development of sporadic T-cell chronic leukemias is supported by the finding of loss of heterozygosity at 11q22-23 and ATM mutations in leukemias carrying TCL-1 rearrangements. Approximately 14% of B-cell chronic lymphocytic leukemia (B-CLL), the most common adult leukemia, carry deletions of the long arm of chromosome 11 at 11q22-23. Loss of heterozygosity at 11q22-23 and, more recently, absence of ATM protein, have been associated with poor prognosis in B-CLL. To determine whether the ATM gene is altered in B-CLL, we have sequenced individual ATM exons in six B-CLL cases. We show that the ATM gene is mutated in a fraction of B-CLLs and that mutations can be present in the germ line of patients, suggesting that ATM heterozygotes may be predisposed to B-CLL.
位于11号染色体长臂11q22 - 23的ATM基因突变会导致共济失调毛细血管扩张症，这是一种常染色体隐性疾病，与恶性肿瘤尤其是淋巴瘤的发病率增加相关。11q22 - 23杂合性缺失以及携带TCL - 1重排的白血病中ATM突变的发现，支持了ATM在散发性T细胞慢性白血病发生发展中的作用。大约14%的B细胞慢性淋巴细胞白血病（B - CLL），即最常见的成人白血病，存在11号染色体长臂11q22 - 23缺失。11q22 - 23杂合性缺失以及最近发现的ATM蛋白缺失，与B - CLL的不良预后相关。为了确定ATM基因在B - CLL中是否发生改变，我们对6例B - CLL病例的单个ATM外显子进行了测序。我们发现部分B - CLL中ATM基因发生了突变，并且这些突变可能存在于患者的种系中，这表明ATM杂合子可能易患B - CLL。
