title: [Multiregion sequencing reveals intratumor heterogeneity in esophageal squamous cell carcinoma].
abstract: 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.
authors.affiliation: Translational Medical Center, Zhengzhou Central Hospital, Zhengzhou 450007, China.
authors.forename: W
authors.initials: W
authors.lastname: Cao
authors.affiliation: Henan Province Academician and Expert Workstation, Zhengzhou Central Hospital, Zhengzhou 450007, China.
authors.forename: W
authors.initials: W
authors.lastname: Wu
authors.affiliation: Medical School, Zhengzhou University, Zhengzhou 450001, China.
authors.forename: M
authors.initials: M
authors.lastname: Yan
authors.affiliation: Henan Province Academician and Expert Workstation, People's Hospital of Zhengzhou, Zhengzhou 450053, China.
authors.forename: F
authors.initials: F
authors.lastname: Tian
authors.affiliation: Department of Surgery, Zhengzhou Central Hospital, Zhengzhou 450007, China.
authors.forename: H S
authors.initials: HS
authors.lastname: Liu
authors.affiliation: Department of Pathology, Linzhou Cancer Hospital, Linzhou 456550, China.
authors.forename: J W
authors.initials: JW
authors.lastname: Wang
authors.affiliation: Department of Pathology, Zhengzhou Central Hospital, Zhengzhou 450007, China.
authors.forename: Q W
authors.initials: QW
authors.lastname: Zhang
authors.affiliation: Department of Otolaryngology, Zhengzhou Central Hospital, Zhengzhou 450007, China.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Zhengzhou Central Hospital, Zhengzhou 450007, China.
authors.forename: M
authors.initials: M
authors.lastname: Li
mesh_terms: D002294:Carcinoma, Squamous Cell; D055028:Comparative Genomic Hybridization; D004938:Esophageal Neoplasms; D000077277:Esophageal Squamous Cell Carcinoma; D018628:Gene Dosage; D023281:Genomics; D006801:Humans; D008198:Lymph Nodes; D008207:Lymphatic Metastasis; D009154:Mutation; D010802:Phylogeny