title: Genomic profiling of 766 cancer-related genes in archived esophageal normal and carcinoma tissues.
abstract: We employed the BeadArraytrade mark technology to perform a genetic analysis in 33 formalin-fixed, paraffin-embedded (FFPE) human esophageal carcinomas, mostly squamous-cell-carcinoma (ESCC), and their adjacent normal tissues. A total of 1,432 single nucleotide polymorphisms (SNPs) derived from 766 cancer-related genes were genotyped with partially degraded genomic DNAs isolated from these samples. This directly targeted genomic profiling identified not only previously reported somatic gene amplifications (e.g., CCND1) and deletions (e.g., CDKN2A and CDKN2B) but also novel genomic aberrations. Among these novel targets, the most frequently deleted genomic regions were chromosome 3p (including tumor suppressor genes FANCD2 and CTNNB1) and chromosome 5 (including tumor suppressor gene APC). The most frequently amplified genomic region was chromosome 3q (containing DVL3, MLF1, ABCC5, BCL6, AGTR1 and known oncogenes TNK2, TNFSF10, FGF12). The chromosome 3p deletion and 3q amplification occurred coincidently in nearly all of the affected cases, suggesting a molecular mechanism for the generation of somatic chromosomal aberrations. We also detected significant differences in germline allele frequency between the esophageal cohort of our study and normal control samples from the International HapMap Project for 10 genes (CSF1, KIAA1804, IL2, PMS2, IRF7, FLT3, NTRK2, MAP3K9, ERBB2 and PRKAR1A), suggesting that they might play roles in esophageal cancer susceptibility and/or development. Taken together, our results demonstrated the utility of the BeadArray technology for high-throughput genetic analysis in FFPE tumor tissues and provided a detailed genetic profiling of cancer-related genes in human esophageal cancer.
authors.affiliation: Illumina Inc., San Diego, CA 92121, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Liping
authors.initials: L
authors.lastname: Guo
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Peiffer
authors.forename: Lixin
authors.initials: L
authors.lastname: Zhou
authors.forename: Owen Tsan Mo
authors.initials: OT
authors.lastname: Chan
authors.forename: Marina
authors.initials: M
authors.lastname: Bibikova
authors.forename: Eliza
authors.initials: E
authors.lastname: Wickham-Garcia
authors.forename: Shih-Hsin
authors.initials: SH
authors.lastname: Lu
authors.forename: Qimin
authors.initials: Q
authors.lastname: Zhan
authors.forename: Jessica
authors.initials: J
authors.lastname: Wang-Rodriguez
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Jian-Bing
authors.initials: JB
authors.lastname: Fan
mesh_terms: D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D002681:China / Q000453:epidemiology; D002869:Chromosome Aberrations; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D004947:Esophagus / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling; D005838:Genotype; D006801:Humans; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*