【摘要】 癌是一种涉及多基因变异的遗传异质性疾病,涉及多种生物学功能通路中不同基因的遗传变异。因此,识别癌基因是一项富有挑战性的工作。提出通过寻找在癌样本中突变显著共发生的基因筛选候选癌基因的方法。应用该方法,通过分析蛋白激酶基因在癌组织中的突变谱数据,发现了167个显著共发生突变的基因对,包含85个基因。分析这167个基因对发现:(1)发生共突变的基因富集已知的癌基因;(2)共突变基因对倾向于共扰动与癌症相关的通路对。以上结果提示,在癌样本中显著共发生突变的基因倾向于候选癌基因;在癌发生过程中起重要作用的基因倾向于协同扰动不同的癌相关细胞生物学过程。更多还原

【Abstract】 Cancer is a heterogeneous disease involving functional abnormalities of different genes in multiple biological pathways.Therefore,identifying genes whose mutations are causally implicated in oncogenesis is a challenging task in cancer research.Here,we proposed an approach to identify cancer genes by seeking pairs of genes with co-occurring mutations in cancer genomes.Applying the approach to analyze a dataset of somatic mutation of kinase genes in cancer tissues,we found 167 co-mutated gene pairs consisting of 85 genes.By analyzing these co-mutated gene pairs,we found that(1) the co-mutated genes are enriched with known cancer genes;(2) the co-mutated genes tend to co-disrupt cancer-related functional pathways.Our results indicate that genes co-mutating in cancer samples tend to be cancer genes,and mutations of multiple genes participating in different pathways may be synergistic in conferring selection advantages to cancer cells.更多还原