在吸烟者和从未吸烟者中非小细胞肺癌的基因组景观
Ramaswamy Govindan1, Li Ding, Malachi Griffith
1Department of Internal Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Cell
|September 18, 2012
概括
这项研究对非小细胞肺癌 (NSCLC) 瘤进行了测序,在吸烟者中发现了显著更多的突变. 确定了关键的基因和通路,为肺癌治疗提供了潜在的新药标.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 分子生物学分子生物学
背景情况:
- 非小细胞肺癌 (NSCLC) 仍然是全球癌症相关死亡的主要原因.
- 了解NSCLC的基因组景观对于开发有效的向疗法至关重要.
研究的目的:
- 为了全面分析NSCLC瘤的全基因组和转录组.
- 在NSCLC中识别新的遗传变异,突变模式和潜在的治疗点.
主要方法:
- 来自17名NSCLC患者的瘤和相邻正常组织的全基因组和转录组测序.
- 深度数字测序以分析克隆性.
- 生物信息分析用于识别突变,indels,基因融合和途径改变.
主要成果:
- 鉴定了3,726个点突变和>90个indels,在吸烟者中突变频率高于10倍.
- 在染色质修饰,DNA修复,DACH1,CFTR,RELN,ABCB5和HGF中发现了新的改变.
- 发现了各种各样的克隆性模式,并确定了14个融合 (包括 在创始克隆中发现了EGFR和KRAS突变.
- 揭示了细胞循环和JAK-STAT通路的显著变化,有54个潜在的向基因.
结论:
- 吸烟是NSCLC突变发生的一个主要驱动因素.
- 特定途径和基因的基因组改变为向的NSCLC疗法提供了机会.
- 在EGFR和KRAS的创始突变表明在早期瘤发生中的作用.
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