英国科学家宣布，他们首次成功绘制出肺癌和皮肤癌完整的基因图谱，英国医学科学院院长约翰·贝尔表示，这是最近十多年癌症研究和治疗方面“变革性”的进步，相关研究发表在17日出版的《自然》杂志上。
该研究的领导者、英国癌症基因组计划领导人之一迈克·斯特拉顿认为，绘制出完整的癌症基因图谱意味着，医生能够更早地发现人体癌细胞，让病人据此进行预防；并且只需要进行一个简单的血液测试，然后根据每个个体的不同情况，制定出 “个性化”的治疗方案；也能让科学家尽快研发出针对特定基因变异的抗癌药物。
科学家们在这两份最新绘制出的图谱中记录下了人体细胞数千种基因突变，正是这些基因突变导致细胞癌化，产生癌症。
英国慈善癌症研究会负责人哈帕尔·库玛表示，下一步将是从这几千种变异中找出哪些变异基因真正导致癌细胞的形成和扩散，哪些变异基因是偶发的，以便让我们更好地找到方式来进行纠正和预防。绘制完整的癌细胞基因图谱还有助于为健康人群提供MoT血样测试，以测验出他们的DNA是否有可能已产生病变。
有关专家指出，尽管环境因素对癌症的影响巨大，但从根本讲，癌症是一种DNA缺陷疾病。DNA缺陷会导致基因变异（有些由致癌物诱发），从而使某些细胞开始不受控制地分裂，然后在体内扩散。越来越多的研究表明，癌症并非单一疾病，每种癌症都包括大量由不同类型基因变异导致的不同亚种类别，需要分别对症治疗。
目前的这两份图谱是国际癌症基因组协会的“癌症基因图谱项目”的首批成果。国际癌症基因组协会于2008年4月29日成立，它集中国、美国、英国等10个成员的科学家之力，绘制完整的人类癌症基因图谱。目前该组织计划投资10亿美元，用10年时间详细研究可导致50种癌症的变异基因，绘制出这些基因的全图谱。
该协会计划在每种癌症研究中，提取500名该类型癌症患者的癌细胞并对其中的基因进行测序，然后将结果与健康细胞基因的编码作比对，以便确定哪些变异基因真正导致癌细胞的形成和扩散，哪些变异基因是偶发的。
如果人类癌症基因图谱绘制成功，可望开辟癌症个性化治疗新时代。届时医生将能准确知道患者肿瘤生长和扩散的具体基因因素，从而使选择针对特定癌症个体的治疗方法更加容易。这项计划还有助于设计出以癌细胞遗传弱点为靶标的新药。
A comprehensive catalogue of somatic mutations from a human cancer genome
All cancers carry somatic mutations.A subset of these somatic alterations,termed driver mutations, confer selective growth advantage and are implicated in cancer development,whereas the remainder are passengers.Here we have sequenced the genomes of a malignant melanoma and a lymphoblastoid cell line from the same person,providing the first comprehensive catalogue of somatic mutations from an individual cancer.The catalogue provides remarkable insights into the forces that have shaped this cancer genome. The dominant mutational signature reflects DNA damage due to ultraviolet light exposure,a known risk factor for malignant melanoma,whereas the uneven distribution of mutations across the genome,with a lower prevalence in gene footprints,indicates that DNA repair has been preferentially deployed towards transcribed regions.The results illustrate the power of a cancer genome sequence to reveal traces of the DNA damage, repair,mutation and selection processes that were operative years before the cancer became symptomatic.
A small-cell lung cancer genome with complex signatures of tobacco exposure
Cancer is driven by mutation.Worldwide,tobacco smoking is the principal lifestyle exposure that causes cancer,exerting carcinogenicity through >60 chemicals that bind and mutate DNA.Using massively parallel sequencing technology,we sequenced a small-cell lung cancer cell line,NCI-H209,to explore the mutational burden associated with tobacco smoking.A total of 22,910 somatic substitutions were identified,including 134 in coding exons.Multiple mutation signatures testify to the cocktail of carcinogens in tobacco smoke and their proclivities for particular bases and surrounding sequence context.Effects of transcription-coupled repair and a second,more general,expression-linked repair pathway were evident.We identified a tandem duplication that duplicates exons 3–8 of CHD7 in frame, and another two lines carrying PVT1–CHD7 fusion genes,indicating that CHD7 may be recurrently rearranged in this disease.These findings illustrate the potential for next-generation sequencing to provide unprecedented insights into mutational processes,cellular repair pathways and gene networks associated with cancer.
