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Consistent and differential genetic aberrations between esophageal dysplasia and squamous cell carcinoma detected by array comparative genomic hybridization. 2013

Zhi-Zhou Shi, and Li Shang, and Yan-Yi Jiang, and Jia-Jie Hao, and Yu Zhang, and Tong-Tong Zhang, and De-Chen Lin, and Shu-Guang Liu, and Bo-Shi Wang, and Ting Gong, and Qi-Min Zhan, and Ming-Rong Wang

Authors' Affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

OBJECTIVE Our aim was to identify frequent genomic aberrations in both esophageal squamous cell carcinoma (ESCC) and esophageal dysplasia and to discover important copy number-driving genes and microRNAs (miRNA) in ESCC. METHODS We conducted array-based comparative genomic hybridization (array CGH) on 59 ESCC resection samples and 16 dysplasia biopsy samples. Expression of genes at 11q13.3 was analyzed by real-time PCR (RT-PCR) and immunohistochemistry (IHC). Integrated analysis was conducted to identify genes or miRNAs with copy number-expression correlations. RESULTS Array CGH identified 11 amplifications and eight homozygous deletions in ESCC. Integrated analysis of array CGH data with matched gene expression microarray data showed that 90 overexpressed genes and 24 underexpressed genes were consistent with DNA copy number changes, including 12 copy number-driving miRNAs. In esophageal dysplasia, six gains, four losses, 12 amplifications, and four homozygous deletions were detected. Amplifications of 7p11.2 and 11q13.2-11q13.3 (CCND1) and homozygous deletion at 9p21.3 (CDKN2A) were consistent genomic changes in both dysplasia and carcinoma. ANO1 at 11q13.3 was overexpressed at the mRNA and protein levels in tumors, and higher mRNA expression was correlated with the copy number increase. In particular, ANO1 expression was elevated in moderate dysplasia compared with normal esophageal epithelium. IHC revealed that ANO1 overexpression was positively correlated with lymph node metastasis and advanced clinical stage. Knockdown of ANO1 significantly inhibited the proliferation of KYSE30 and KYSE510 cells. CONCLUSIONS Copy number aberrations in both esophageal dysplasia and ESCC may be useful as potential biomarkers for early detection. In addition, ANO1 may be a candidate target gene in esophageal tumorigenesis.

UI	MeSH Term	Description	Entries
D011230	Precancerous Conditions	Pathological conditions that tend eventually to become malignant.	Preneoplastic Conditions,Condition, Preneoplastic,Conditions, Preneoplastic,Preneoplastic Condition,Condition, Precancerous,Conditions, Precancerous,Precancerous Condition
D002294	Carcinoma, Squamous Cell	A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed)	Carcinoma, Epidermoid,Carcinoma, Planocellular,Carcinoma, Squamous,Squamous Cell Carcinoma,Carcinomas, Epidermoid,Carcinomas, Planocellular,Carcinomas, Squamous,Carcinomas, Squamous Cell,Epidermoid Carcinoma,Epidermoid Carcinomas,Planocellular Carcinoma,Planocellular Carcinomas,Squamous Carcinoma,Squamous Carcinomas,Squamous Cell Carcinomas
D002869	Chromosome Aberrations	Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS.	Autosome Abnormalities,Cytogenetic Aberrations,Abnormalities, Autosome,Abnormalities, Chromosomal,Abnormalities, Chromosome,Chromosomal Aberrations,Chromosome Abnormalities,Cytogenetic Abnormalities,Aberration, Chromosomal,Aberration, Chromosome,Aberration, Cytogenetic,Aberrations, Chromosomal,Aberrations, Chromosome,Aberrations, Cytogenetic,Abnormalities, Cytogenetic,Abnormality, Autosome,Abnormality, Chromosomal,Abnormality, Chromosome,Abnormality, Cytogenetic,Autosome Abnormality,Chromosomal Aberration,Chromosomal Abnormalities,Chromosomal Abnormality,Chromosome Aberration,Chromosome Abnormality,Cytogenetic Aberration,Cytogenetic Abnormality
D004938	Esophageal Neoplasms	Tumors or cancer of the ESOPHAGUS.	Cancer of Esophagus,Esophageal Cancer,Cancer of the Esophagus,Esophagus Cancer,Esophagus Neoplasm,Neoplasms, Esophageal,Cancer, Esophageal,Cancer, Esophagus,Cancers, Esophageal,Cancers, Esophagus,Esophageal Cancers,Esophageal Neoplasm,Esophagus Cancers,Esophagus Neoplasms,Neoplasm, Esophageal,Neoplasm, Esophagus,Neoplasms, Esophagus
D004947	Esophagus	The muscular membranous segment between the PHARYNX and the STOMACH in the UPPER GASTROINTESTINAL TRACT.
D005784	Gene Amplification	A selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes. It occurs naturally via the excision of a copy of the repeating sequence from the chromosome and its extrachromosomal replication in a plasmid, or via the production of an RNA transcript of the entire repeating sequence of ribosomal RNA followed by the reverse transcription of the molecule to produce an additional copy of the original DNA sequence. Laboratory techniques have been introduced for inducing disproportional replication by unequal crossing over, uptake of DNA from lysed cells, or generation of extrachromosomal sequences from rolling circle replication.	Amplification, Gene
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077277	Esophageal Squamous Cell Carcinoma	A carcinoma that originates usually from cells on the surface of the middle and lower third of the ESOPHAGUS. Tumor cells exhibit typical squamous morphology and form large polypoid lesions. Mutations in RNF6, LZTS1, TGFBR2, DEC1, and WWOX1 genes are associated with this cancer.	Oesophageal Squamous Cell Carcinoma
D015870	Gene Expression	The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.	Expression, Gene,Expressions, Gene,Gene Expressions
D017353	Gene Deletion	A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.	Deletion, Gene,Deletions, Gene,Gene Deletions