Zhonghua zhong liu za zhi [Chinese journal of oncology] · 2016
[Multiregion sequencing reveals intratumor heterogeneity in esophageal squamous cell carcinoma].
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Cao W, Wu W, Yan M, Tian F, Liu H S, Wang J W, Zhang Q W, Li Y J, Li M
Аннотация
OBJECTIVE: To study the intratumor heterogeneity of esophageal squamous cell carcinoma (ESCC).
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: Sequence analysis of whole genome exon in multiple regions can provide strong evidence for genomic heterogeneity in esophageal squamous cell carcinoma.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: Sequence analysis of whole genome exon in multiple regions can provide strong evidence for genomic heterogeneity in esophageal squamous cell carcinoma.