Department of Science and Biotechnology, American Medical Association, Chicago, Illinois.
Health and Science Group, American Medical Association, Chicago, Illinois.
JAMA Intern Med. 2014 Feb 1;174(2):275-80. doi: 10.1001/jamainternmed.2013.12048.
With increased speed and decreased costs, next-generation gene sequencing has the potential to improve medical care by making possible widespread evaluation of patients' genomes in clinical settings. The entire genome of an individual can now be sequenced in less than 1 week at a cost of $5000 to $10,000; the cost will continue to decline. Analyses based on next-generation sequencing include whole-genome sequencing and whole-exome sequencing; DNA sequences that encode proteins are collectively known as the exome. In some instances, whole genome and whole-exome sequencing have already helped to accurately diagnose diseases with atypical manifestations, that are difficult to diagnose using clinical or laboratory criteria alone, or that otherwise require extensive or costly evaluation. For some patients with malignant neoplasms, next-generating sequencing can improve tumor classification, diagnosis, and management. Many challenges remain, however, such as the storage and interpretation of vast amounts of sequence data, training physicians and other health care professionals whose knowledge of genetics may be insufficient, effective genetic counseling and communication of results to patients, and establishing standards for the appropriate use of the technology. Rigorous studies are needed to assess the utility of whole-genome and whole-exome sequencing in large groups of patients, including comparative studies with other approaches to screening and diagnosis, and the evaluation of clinical end points and health care costs. The successes to date have been in single cases or in very small groups of patients. At present, although whole-genome or whole-exome sequencing show great promise, they should be incorporated into patient care only in limited clinical situations.
随着速度的提高和成本的降低，下一代基因测序有可能通过在临床环境中广泛评估患者的基因组，从而改善医疗保健。现在，个体的整个基因组可以在不到 1 周的时间内以 5000 美元至 10000 美元的成本完成测序；成本将继续下降。基于下一代测序的分析包括全基因组测序和全外显子组测序；编码蛋白质的 DNA 序列统称为外显子。在某些情况下，全基因组和全外显子组测序已经帮助准确诊断出临床表现不典型、仅使用临床或实验室标准难以诊断或需要广泛或昂贵评估的疾病。对于一些恶性肿瘤患者，下一代测序可以改善肿瘤分类、诊断和管理。然而，仍然存在许多挑战，例如大量序列数据的存储和解释、培训可能缺乏遗传学知识的医生和其他医疗保健专业人员、有效的遗传咨询和向患者传达结果，以及建立技术的适当使用标准。需要进行严格的研究来评估全基因组和全外显子组测序在大量患者中的效用，包括与其他筛查和诊断方法的比较研究，以及评估临床终点和医疗保健成本。迄今为止的成功案例都是在单个病例或非常小的患者群体中。目前，尽管全基因组或全外显子组测序显示出巨大的潜力，但仅在有限的临床情况下才应将其纳入患者护理。
