Cao W, Wu W, Yan M, Tian F, Liu H S, Wang J W, Zhang Q W, Li Y J, Li M
Translational Medical Center, Zhengzhou Central Hospital, Zhengzhou 450007, China.
Henan Province Academician and Expert Workstation, Zhengzhou Central Hospital, Zhengzhou 450007, China.
Zhonghua Zhong Liu Za Zhi. 2016 Sep 23;38(9):660-6. doi: 10.3760/cma.j.issn.0253-3766.2016.09.005.
To study the intratumor heterogeneity of esophageal squamous cell carcinoma (ESCC).
We used whole-exome sequencing and array-based comparative genomic hybridization to profile mutations and changes in copy number from 11 regions within 2 cases of ESCC and from the metastatic lymph nodes.
The numbers of somatic single nuclear polymorphisms (SNPs) in 4 regions within the tumors in case 1 and case 2 were 93±17 and 124±28, respectively. The majority of SNPs were non synonymous mutations, synonymous mutations, nonsense mutations and splicing junction mutations. The average indels in the 4 tumor regions of case 1 and case 2 were 40±6 and 51±3, respectively. These small indels mainly occurred in exonic (frame-shift and non-frame-shift), untranslational regions of genes and splicing junction regions. All regions from a tumor exhibitedo bvious heterogeneity, and mutational similarity of all four regions within a tumor was less than 25%. Furthermore, gene copy number alteration (gain or loss) varied among multiple regions of a tumor, and the similarity of gene copy number was less than 20%. Phylogenetic analysis of the somatic mutation frequency suggests that multiple, genomic heterogeneous clones co-exist within a primary ESCC, and metastatic subclones may evolve from the primary non-metastatic parental clone. These results indicated that a single-region sampling can not reflect the architecture of the genomic landscape of mutations in ESCC tumors.
Sequence analysis of whole genome exon in multiple regions can provide strong evidence for genomic heterogeneity in esophageal squamous cell carcinoma.
研究食管鳞状细胞癌（ESCC）的肿瘤内异质性。
我们使用全外显子组测序和基于芯片的比较基因组杂交技术，对2例ESCC及其转移淋巴结的11个区域的突变和拷贝数变化进行分析。
病例1和病例2肿瘤内4个区域的体细胞单核苷酸多态性（SNP）数量分别为93±17和124±28。大多数SNP为非同义突变、同义突变、无义突变和剪接连接突变。病例1和病例2的4个肿瘤区域的平均插入缺失分别为40±6和51±3。这些小的插入缺失主要发生在外显子（移码和非移码）、基因的非翻译区和剪接连接区。肿瘤的所有区域均表现出明显的异质性，肿瘤内所有四个区域的突变相似性小于25%。此外，肿瘤的多个区域之间基因拷贝数改变（增加或减少）各不相同，基因拷贝数的相似性小于20%。体细胞突变频率的系统发育分析表明，原发性ESCC内存在多个基因组异质性克隆，转移亚克隆可能从原发性非转移亲本克隆进化而来。这些结果表明，单区域采样不能反映ESCC肿瘤突变的基因组景观结构。
对多个区域的全基因组外显子进行序列分析可为食管鳞状细胞癌的基因组异质性提供有力证据。
