Multisample genomic analysis of solid childhood cancers using high resolution SNP-arrays, Whole Exome Sequencing and Targeted Deep Sequencing.

We mapped the prevalence of genetically distinct clones over 248 regions in 54 childhood cancers. This revealed that primary tumors can simultaneously follow up to four evolutionary patterns in different anatomic areas. The most common pattern consists of a fluctuating presence over anatomic space of subclones with very few mutations. The second most common is a surprisingly stable coexistence, over vast areas, of clones with different changes in chromosome numbers. This is contrasted by a third, less frequent, pattern where a novel clone harboring driver mutations or structural chromosome rearrangements completely replaces its progenitor. The fourth and rarest pattern is the local emergence of a myriad of clones with TP53 inactivation. Strikingly, death from disease was limited to tumors exhibiting the two latter, most dynamic patterns.EGA study EGAS00001002662

本研究针对54种儿童癌症的248个病灶区域，绘制了基因特征各异的克隆（genetically distinct clones）的流行率分布图谱。研究结果显示，原发性肿瘤可在不同解剖区域同时呈现至多四种演化模式。其中最常见的模式为：突变负荷极低的亚克隆（subclone）在解剖空间内的存在状态呈波动特征。第二常见的模式则是：在大范围解剖区域内，染色体数目存在差异的克隆可稳定共存，该现象颇为出人意料。与之形成鲜明对比的是第三种较为少见的模式：携带驱动突变或染色体结构重排的新型克隆会完全取代其亲本克隆。第四种亦是最为罕见的模式为：TP53基因（TP53）失活的大量克隆在局部区域涌现。值得注意的是，因疾病死亡的病例仅局限于呈现后两种最具动态性演化特征的肿瘤。相关研究数据收录于欧洲基因组档案（European Genome Archive）研究编号EGAS00001002662。