title: Genomic copy-number alterations of MYC and FHIT genes are associated with survival in esophageal squamous-cell carcinoma.
abstract: Esophageal squamous-cell carcinoma (ESCC) is one of the most common cancers and is associated with a poor prognosis. Studies are warranted on the clinical relevance of its genomic copy-number alterations (CNA) as prognosticators for ESCC. In the present study, we first screened recurrent CNA by array-based comparative genomic hybridization using an in-house focused bacterial artificial chromosome-based array for 108 loci in 45 ESCC specimens. We detected 14 regions showing recurrent (>20%) CNA (4 losses and 10 gains) by array-based comparative genomic hybridization in the first cohort. Among them, loss of 3p14.2 and gain of 8q24.21 for the FHIT and MYC genes, respectively, and the accumulation of those two CNA (higher FM-CNA scores) were significantly associated with a worse overall survival (OS) in the first cohort (P = 0.0273, P = 0.0356 and P = 0.0089, respectively). In the independent validation cohort of 92 resected ESCC cases, loss of FHIT, gain of MYC and higher FM-CNA scores determined by a quantitative genomic PCR-based copy-number analysis were associated with a worse OS (P = 0.0011, P = 0.0104 and P = 0.0008, respectively) and disease-free survival (P = 0.0038, P = 0.0132 and P = 0.0021, respectively). In addition, the Cox model showed the presence of either CNA to be an independent prognosticator for OS and disease-free survival in the validation cohort (P = 0.0120 and P = 0.0255, respectively). These results suggest that CNA of MYC and FHIT are poor prognostic markers, and risk stratification based on the copy-number status of those genes is useful to select the optimal treatment strategy in resected ESCC patients.
authors.affiliation: Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Miyawaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawachi
authors.forename: Akishi
authors.initials: A
authors.lastname: Ooi
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Eishi
authors.forename: Tatsuyuki
authors.initials: T
authors.lastname: Kawano
authors.forename: Johji
authors.initials: J
authors.lastname: Inazawa
authors.forename: Issei
authors.initials: I
authors.lastname: Imoto
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality; D043171:Chromosomal Instability; D055028:Comparative Genomic Hybridization; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000401:mortality; D005500:Follow-Up Studies; D016259:Genes, myc; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction; D016019:Survival Analysis; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase