title: Recurrent amplification of MYC and TNFRSF11B in 8q24 is associated with poor survival in patients with gastric cancer.
abstract: BACKGROUND
  Gastric cancer (GC) is an aggressive malignancy whose mechanisms of development and progression are poorly understood. The identification of prognosis-related genomic loci and genes may suffer from the relatively small case numbers and a lack of systematic validation in previous studies.
  
  
  METHODS
  Array-based comparative genomic hybridization (aCGH) coupled with patient clinical information was applied to identify prognosis-related loci and genes with high-frequency recurrent gains in 129 GC patients. The candidate loci and genes were then validated using an independent cohort of 384 patients through branched DNA signal amplification analysis (QuantiGene assays).
  
  
  RESULTS
  In the 129 patients, a copy number gain of three chromosome regions-namely, 8q22 (including ESRP1 and CCNE2), 8q24 (including MYC and TNFRSF11B), and 20q11-q13 (including SRC, MMP9, and CSE1L)--conferred poor survival for patients. In addition, the correlation between the branched DNA signal amplification analysis results and the aCGH results was analyzed in 73 of these 129 patients, and MYC, TNFRSF11B, ESRP1, CSE1L, and MMP9 were found to be well correlated. Further validation using an independent cohort (n = 384) verified that only MYC and TNFRSF11B within 8q24 are related to survival. Patients with gains in both MYC and TNFRSF11B had poorer survival than those with no gains, particularly those with noncardia GC. Gains in both of these genes were also a significant independent prognostic indicator.
  
  
  CONCLUSIONS
  Our results revealed that copy number gains in MYC and TNFRSF11B located at 8q24 are associated with survival in GC, particularly noncardia GC.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Tissue Bank, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
authors.forename: Yiqiang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Surgery, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
authors.forename: Duanfang
authors.initials: D
authors.lastname: Shao
authors.affiliation: Asia and Emerging Markets Innovative Medicine, AstraZeneca R&D, Shanghai, 201203, China.
authors.forename: Ziliang
authors.initials: Z
authors.lastname: Qian
authors.affiliation: Asia and Emerging Markets Innovative Medicine, AstraZeneca R&D, Shanghai, 201203, China.
authors.forename: Zhengwei
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Asia and Emerging Markets Innovative Medicine, AstraZeneca R&D, Shanghai, 201203, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Surgery, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Xing
authors.affiliation: Department of Surgery, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Surgery, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Du
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Tissue Bank, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Tissue Bank, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
authors.forename: Yingai
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Surgery, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Dong
authors.affiliation: Department of Surgery, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
authors.forename: Ziyu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Surgery, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
authors.forename: Aiwen
authors.initials: A
authors.lastname: Wu
authors.affiliation: Department of Surgery, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Surgery, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
authors.forename: Zhaode
authors.initials: Z
authors.lastname: Bu
authors.affiliation: Department of Surgery, Peking University Cancer Hospital and Institute, Beijing, 100142, China.
authors.forename: Xianglong
authors.initials: X
authors.lastname: Zong
authors.affiliation: Asia and Emerging Markets Innovative Medicine, AstraZeneca R&D, Shanghai, 201203, China.
authors.forename: Guanshan
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Asia and Emerging Markets Innovative Medicine, AstraZeneca R&D, Shanghai, 201203, China.
authors.forename: Qunsheng
authors.initials: Q
authors.lastname: Ji
authors.affiliation: Department of Surgery, Peking University Cancer Hospital and Institute, Beijing, 100142, China. 13661176007@163.com.
authors.forename: Xian-zi
authors.initials: XZ
authors.lastname: Wen
authors.affiliation: Department of Surgery, Peking University Cancer Hospital and Institute, Beijing, 100142, China. zlhzlh@hotmail.com.
authors.forename: Lian-hai
authors.initials: LH
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Peking University Cancer Hospital and Institute, Beijing, 100142, China. jiafuj@gmail.com.
authors.forename: Jia-fu
authors.initials: JF
authors.lastname: Ji
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002898:Chromosomes, Human, Pair 8; D015331:Cohort Studies; D055028:Comparative Genomic Hybridization / Q000379:methods; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D016259:Genes, myc; D006801:Humans; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000235:genetics*; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D016019:Survival Analysis
chemical_list: D053244:Osteoprotegerin; C506030:TNFRSF11B protein, human
keywords: 8q24; Gastric cancer; MYC; Survival; TNFRSF11B