Absence of mutations in the ATM gene in breast cancer patients with severe responses to radiotherapy.
Absence of mutations in the ATM gene in breast cancer patients with severe responses to radiotherapy.
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DOI：
10.1038/bjc.1997.593
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发表时间：
1997
影响因子：
8.8
通讯作者：
Scott D
中科院分区：
文献类型：
--
作者：
Appleby JM;Barber JB;Levine E;Varley JM;Taylor AM;Stankovic T;Heighway J;Warren C;Scott D
癌症放射治疗的有效性受到小部分（约5%）患者在标准放射治疗后持续严重正常组织损伤的影响。需要进行预测性测试来识别这些高度辐射敏感的病例。患有罕见的、reckless遗传的、癌症倾向综合征共济失调-毛细血管扩张症（A-T）的患者在放射治疗后维持极其严重的正常组织坏死，并且他们培养的细胞也是高度放射敏感的。临床上正常的A-T基因携带者（杂合子）患乳腺癌的风险增加，约占所有乳腺癌病例的4%，并显示出体外细胞放射敏感性的适度增加。有人认为，相当大比例的高放射敏感性（HR）乳腺癌患者可能是A-T杂合子，A-T基因突变的筛查可用作预测性试验。我们已经在一组对放射治疗有不良反应的癌症患者中验证了这一假设。16例HR乳腺癌患者主要表现为急性反应（7例HR患者患有其他癌症），使用限制性内切酶指纹分析检测ATM突变。未检测到在专性A-T杂合子中发现的典型突变。如果4%的乳腺癌病例是A-T基因携带者的估计是正确的，那么ATM突变并不赋予临床放射敏感性。这些早期结果表明，在癌症患者中筛查ATM突变可能对预测不良反应没有价值。
The effectiveness of cancer radiotherapy is compromised by the small proportion (approximately 5%) of patients who sustain severe normal tissue damage after standard radiotherapy treatments. Predictive tests are required to identify these highly radiosensitive cases. Patients with the rare, recessively inherited, cancer-prone syndrome ataxia-telangiectasia (A-T) sustain extremely severe normal tissue necrosis after radiotherapy and their cultured cells are also highly radiosensitive. Clinically normal carriers (heterozygotes) of the A-T gene have an increased risk of breast cancer, account for approximately 4% of all breast cancer cases and show a modest increase in cellular radiosensitivity in vitro. It has been suggested that a substantial proportion of highly radiosensitive (HR) breast cancer patients may be A-T heterozygotes, and that screening for mutations in the A-T gene could be used as a predictive test. We have tested this hypothesis in a group of cancer patients who showed adverse reactions to radiotherapy. Sixteen HR breast cancer patients showing mainly acute reactions (and seven HR patients with other cancers) were tested for ATM mutations using the restriction endonuclease fingerprinting assay. No mutations typical of those found in obligate A-T heterozygotes were detected. If the estimate that 4% of breast cancer cases are A-T gene carriers is correct, then ATM mutations do not confer clinical radiosensitivity. These early results suggest that screening for ATM mutations in cancer patients may not be of value in predicting adverse reactions.