From bench to bedside... but when?
From bench to bedside... but when?
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从长凳到床边......但是什么时候？
作者：
Eng,C
在1994年9月之前，我们癌症家庭诊所的医生坐在有乳腺癌家族史的患者面前，虽然谨慎地预言，一旦第一个乳腺癌易感基因BRCA 1被克隆出来，我们将以不同的方式进行临床癌症遗传学研究。1994年秋天，BRCA 1被送到了科学家、临床癌症遗传学家、患者和好奇的旁观者的期待世界（三木等人，1994）。由于人类基因组计划及其附带的技术和信息，第二个乳腺癌易感基因BRCA 2被定位并分离出来（伍斯特等人，1994，1995）;其他可能导致乳腺癌易感性的基因，ATM（共济失调-毛细血管扩张）和PTEN（考登综合征）（Savitsky et al. 1995; Nelen et al. 1996; Liaw et al. 1997）。分子肿瘤学的时代已经到来，但是是什么让今天的前沿基因发现成为明天的临床实践呢？最重要的标准是对患者的益处或潜在益处，即基因检测改变了临床治疗。其他标准（表1）包括突变检测的容易性，大多数患有特定遗传性癌症综合征的人在同一基因内含有突变，突变分析可以预测癌症风险，并且可以进行有效的监测或有效的预防措施。两种遗传性癌症综合征说明了翻译最新分子遗传学的痛苦和狂喜--向米开朗琪罗道歉--
Prior to September 1994, we physicians in Cancer Family Clinic sat in front of patients who had family histories of breast cancer, prophesying, albeit cautiously, that we would be practicing clinical cancer genetics differently once the first breast cancer susceptibility gene, BRCA1 was cloned. In the autumn of 1994, BRCA1 was delivered into an expectant world of scientists, clinical cancer geneticists, patients, and curious onlookers (Miki et al. 1994). In rapid succession, thanks to the Human Genome Project and its fallout technology and information, the second breast cancer susceptiblity gene BRCA2 was mapped and isolated (Wooster et al. 1994, 1995); other genes that may lend susceptiblity to breast cancer, ATM (ataxia-telangiectasia) and PTEN (Cowden syndrome), ensued (Savitsky et al. 1995; Nelen et al. 1996; Liaw et al. 1997). The era of molecular oncology had arrived.But what makes cutting-edge genetic findings of today clinical practice tomorrow? The most important criterion is benefit or potential benefit to the patient—that genetic tests result in altered clinical management. Other criteria (Table 1) include ease of mutation detection, the majority of people with a specific inherited cancer syndrome contain mutations within the same gene, the mutation analysis allows prediction of cancer risk, and effective surveillance or effective prophylactic procedures are available. Two inherited cancer syndromes illustrate the agony and ecstasy—apologies to Michelangelo—of translating the latest molecular genetic