Tumor Biology

, Volume 36, Issue 10, pp 7385–7394 | Cite as

Gene mutations in gastric cancer: a review of recent next-generation sequencing studies

  • Y. Lin
  • Z. Wu
  • W. Guo
  • J. Li


Gastric cancer (GC) is one of the most common malignancies worldwide. Although some driver genes have been identified in GC, the molecular compositions of GC have not been fully understood. The development of next-generation sequencing (NGS) provides a high-throughput and systematic method to identify all genetic alterations in the cancer genome, especially in the field of mutation detection. NGS studies in GC have discovered some novel driver mutations. In this review, we focused on novel gene mutations discovered by NGS studies, along with some well-known driver genes in GC. We organized mutated genes from the perspective of related biological pathways. Mutations in genes relating to genome integrity (TP53, BRCA2), chromatin remodeling (ARID1A), cell adhesion (CDH1, FAT4, CTNNA1), cytoskeleton and cell motility (RHOA), Wnt pathway (CTNNB1, APC, RNF43), and RTK pathway (RTKs, RAS family, MAPK pathway, PIK pathway) are discussed. Efforts to establish a molecular classification based on NGS data which is valuable for future targeted therapy for GC are introduced. Comprehensive dissection of the molecular profile of GC cannot only unveil the molecular basis for GC but also identify genes of clinical utility, especially potential and specific therapeutic targets for GC.


Gastric cancer Gene mutation Next-generation sequencing 



This work was supported by the National Science and Technology Major Projects of China (Grant No.: 2012ZX09303-018-002).

Conflicts of interest



  1. 1.
    McLean MH, El-Omar EM. Genetics of gastric cancer. Nat Rev Gastroenterol Hepatol. 2014;11(11):664–74. doi: 10.1038/nrgastro.2014.143.PubMedCrossRefGoogle Scholar
  2. 2.
    Lauren P. The Two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbio Scand. 1965;64:31–49.CrossRefGoogle Scholar
  3. 3.
    Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747–52. doi: 10.1038/35021093.PubMedCrossRefGoogle Scholar
  4. 4.
    Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014;15(11):1224–35. doi: 10.1016/s1470-2045(14)70420-6.PubMedCrossRefGoogle Scholar
  5. 5.
    Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014;383(9911):31–9. doi: 10.1016/s0140-6736(13)61719-5.PubMedCrossRefGoogle Scholar
  6. 6.
    Qin S. Phase III study of apatinib in advanced gastric cancer: a randomized, double-blind, placebo-controlled trial. J Clin Oncol. 2014;32(15 Suppl):abstr 4003.Google Scholar
  7. 7.
    Lordick F, Kang YK, Chung HC, Salman P, Oh SC, Bodoky G, et al. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol. 2013;14(6):490–9. doi: 10.1016/s1470-2045(13)70102-5.PubMedCrossRefGoogle Scholar
  8. 8.
    Meyerson M, Gabriel S, Getz G. Advances in understanding cancer genomes through second-generation sequencing. Nat Rev Genet. 2010;11(10):685–96.PubMedCrossRefGoogle Scholar
  9. 9.
    Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74. doi: 10.1016/j.cell.2011.02.013.PubMedCrossRefGoogle Scholar
  10. 10.
    Lane DP. Cancer. p53, guardian of the genome. Nature. 1992;358(6381):15–6. doi: 10.1038/358015a0.PubMedCrossRefGoogle Scholar
  11. 11.
    Wang K, Kan J, Yuen ST, Shi ST, Chu KM, Law S, et al. Exome sequencing identifies frequent mutation of ARID1A in molecular subtypes of gastric cancer. Nat Genet. 2011;43(12):1219–23. doi: 10.1038/ng.982.PubMedCrossRefGoogle Scholar
  12. 12.
    Zang ZJ, Cutcutache I, Poon SL, Zhang SL, McPherson JR, Tao J, et al. Exome sequencing of gastric adenocarcinoma identifies recurrent somatic mutations in cell adhesion and chromatin remodeling genes. Nat Genet. 2012;44(5):570–4. doi: 10.1038/ng.2246.PubMedCrossRefGoogle Scholar
  13. 13.
    Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513(7517):202–9. doi: 10.1038/nature13480.CrossRefGoogle Scholar
  14. 14.
    Kakiuchi M, Nishizawa T, Ueda H, Gotoh K, Tanaka A, Hayashi A, et al. Recurrent gain-of-function mutations of RHOA in diffuse-type gastric carcinoma. Nat Genet. 2014;46(6):583–7. doi: 10.1038/ng.2984.PubMedCrossRefGoogle Scholar
  15. 15.
    Wang K, Yuen ST, Xu J, Lee SP, Yan HH, Shi ST, et al. Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer. Nat Genet. 2014;46(6):573–82. doi: 10.1038/ng.2983.PubMedCrossRefGoogle Scholar
  16. 16.
    Chang VY, Federman N, Martinez-Agosto J, Tatishchev SF, Nelson SF. Whole exome sequencing of pediatric gastric adenocarcinoma reveals an atypical presentation of Li-Fraumeni syndrome. Pediatr Blood Cancer. 2013;60(4):570–4. doi: 10.1002/pbc.24316.PubMedCrossRefGoogle Scholar
  17. 17.
    Cristescu R, Lee J, Nebozhyn M, Kim KM, Ting JC, Wong SS, et al. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes. Nat Med. 2015;21(5):449–56. doi: 10.1038/nm.3850.PubMedCrossRefGoogle Scholar
  18. 18.
    Holbrook JD, Parker JS, Gallagher KT, Halsey WS, Hughes AM, Weigman VJ, et al. Deep sequencing of gastric carcinoma reveals somatic mutations relevant to personalized medicine. J Transl Med. 2011;9:119. doi: 10.1186/1479-5876-9-119.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Kang G, Hwang WC, Do IG, Wang K, Kang SY, Lee J, et al. Exome sequencing identifies early gastric carcinoma as an early stage of advanced gastric cancer. PloS One. 2013;8(12), e82770. doi: 10.1371/journal.pone.0082770.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Lee J, van Hummelen P, Go C, Palescandolo E, Jang J, Park HY, et al. High-throughput mutation profiling identifies frequent somatic mutations in advanced gastric adenocarcinoma. PloS One. 2012;7(6):e38892. doi: 10.1371/journal.pone.0038892.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Wong SS, Kim KM, Ting JC, Yu K, Fu J, Liu S, et al. Genomic landscape and genetic heterogeneity in gastric adenocarcinoma revealed by whole-genome sequencing. Nat Commun. 2014;5:5477. doi: 10.1038/ncomms6477.PubMedCrossRefGoogle Scholar
  22. 22.
    Kim TM, Jung SH, Kim MS, Baek IP, Park SW, Lee SH, et al. The mutational burdens and evolutionary ages of early gastric cancers are comparable to those of advanced gastric cancers. J Pathol. 2014;234(3):365–74. doi: 10.1002/path.4401.PubMedCrossRefGoogle Scholar
  23. 23.
    Kim YH, Liang H, Liu X, Lee JS, Cho JY, Cheong JH, et al. AMPKα modulation in cancer progression: multilayer integrative analysis of the whole transcriptome in Asian gastric cancer. Cancer Res. 2012;72(10):2512–21. doi: 10.1158/0008-5472.can-11-3870.PubMedCrossRefGoogle Scholar
  24. 24.
    Lee YS, Cho YS, Lee GK, Lee S, Kim YW, Jho S, et al. Genomic profile analysis of diffuse-type gastric cancers. Genome Biol. 2014;15(4):R55. doi: 10.1186/gb-2014-15-4-r55.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Cerami E, Gao JJ, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, et al. The cBio Cancer Genomics Portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012;2(5):401–4.PubMedCrossRefGoogle Scholar
  26. 26.
    Gao JJ, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013;6(269):l1.CrossRefGoogle Scholar
  27. 27.
    Venkitaraman AR. Cancer susceptibility and the functions of BRCA1 and BRCA2. Cell. 2002;108(2):171–82.PubMedCrossRefGoogle Scholar
  28. 28.
    Chen K, Yang D, Li X, Sun B, Song F, Cao W, et al. Mutational landscape of gastric adenocarcinoma in Chinese: implications for prognosis and therapy. Proc Natl Acad Sci USA. 2015;112(4):1107–12. doi: 10.1073/pnas.1422640112.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Hansford S, Kaurah P, Li-Chang H, Woo M, Senz J, Pinheiro H, et al. Hereditary diffuse gastric cancer syndrome: CDH1 mutations and beyond. JAMA Oncol. 2015;1(1):23–32. doi: 10.1001/jamaoncol.2014.168.PubMedCrossRefGoogle Scholar
  30. 30.
    Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, et al. Mutational landscape and significance across 12 major cancer types. Nature. 2013;502(7471):333–9. doi: 10.1038/nature12634.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Saha A, Wittmeyer J, Cairns BR. Chromatin remodelling: the industrial revolution of DNA around histones. Nat Rev Mol Cell Biol. 2006;7(6):437–47. doi: 10.1038/nrm1945.PubMedCrossRefGoogle Scholar
  32. 32.
    Yaniv M. Chromatin remodeling: from transcription to cancer. Cancer Genet. 2014;207(9):352–7. doi: 10.1016/j.cancergen.2014.03.006.PubMedCrossRefGoogle Scholar
  33. 33.
    Jones S, Li M, Parsons DW, Zhang X, Wesseling J, Kristel P, et al. Somatic mutations in the chromatin remodeling gene ARID1A occur in several tumor types. Hum Mutat. 2012;33(1):100–3. doi: 10.1002/humu.21633.PubMedCrossRefGoogle Scholar
  34. 34.
    Jones S, Wang TL, Shih Ie M, Mao TL, Nakayama K, Roden R, et al. Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma. Science. 2010;330(6001):228–31. doi: 10.1126/science.1196333.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Wiegand KC, Shah SP, Al-Agha OM, Zhao Y, Tse K, Zeng T, et al. ARID1A mutations in endometriosis-associated ovarian carcinomas. N Engl J Med. 2010;363(16):1532–43. doi: 10.1056/NEJMoa1008433.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Nagl Jr NG, Wang X, Patsialou A, Van Scoy M, Moran E. Distinct mammalian SWI/SNF chromatin remodeling complexes with opposing roles in cell-cycle control. EMBO J. 2007;26(3):752–63. doi: 10.1038/sj.emboj.7601541.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Weissman B, Knudsen KE. Hijacking the chromatin remodeling machinery: impact of SWI/SNF perturbations in cancer. Cancer Res. 2009;69(21):8223–30. doi: 10.1158/0008-5472.CAN-09-2166.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Je EM, Lee SH, Yoo NJ, Lee SH. Mutational and expressional analysis of MLL genes in gastric and colorectal cancers with micro satellite instability. Neoplasma. 2013;60(2):188–95. doi: 10.4149/neo_2013_025.PubMedCrossRefGoogle Scholar
  39. 39.
    Fitzgerald RC, Hardwick R, Huntsman D, Carneiro F, Guilford P, Blair V, et al. Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research. J Medical Genet. 2010;47(7):436–44. doi: 10.1136/jmg.2009.074237.CrossRefGoogle Scholar
  40. 40.
    Majewski IJ, Kluijt I, Cats A, Scerri TS, de Jong D, Kluin RJ, et al. An α-E-catenin (CTNNA1) mutation in hereditary diffuse gastric cancer. J Pathol. 2013;229(4):621–9. doi: 10.1002/path.4152.PubMedCrossRefGoogle Scholar
  41. 41.
    Tenedini E, Bernardis I, Artusi V, Artuso L, Roncaglia E, Guglielmelli P, et al. Targeted cancer exome sequencing reveals recurrent mutations in myeloproliferative neoplasms. Leukemia. 2014;28(5):1052–9. doi: 10.1038/leu.2013.302.PubMedCrossRefGoogle Scholar
  42. 42.
    Yu J, Wu WK, Li X, He J, Li XX, Ng SS, et al. Novel recurrently mutated genes and a prognostic mutation signature in colorectal cancer. Gut. 2015;64(4):636–45. doi: 10.1136/gutjnl-2013-306620.PubMedCrossRefGoogle Scholar
  43. 43.
    Wang Y. Wnt/planar cell polarity signaling: a new paradigm for cancer therapy. Mol Cancer Ther. 2009;8(8):2103–9. doi: 10.1158/1535-7163.MCT-09-0282.PubMedCrossRefGoogle Scholar
  44. 44.
    Ward CJ, Wu Y, Johnson RA, Woollard JR, Bergstralh EJ, Cicek MS, et al. Germline PKHD1 mutations are protective against colorectal cancer. Hum Genet. 2011;129(3):345–9. doi: 10.1007/s00439-011-0950-8.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Karlsson R, Pedersen ED, Wang Z, Brakebusch C. Rho GTPase function in tumorigenesis. Biochim Biophys Acta. 2009;1796(2):91–8. doi: 10.1016/j.bbcan.2009.03.003.PubMedGoogle Scholar
  46. 46.
    Wheeler AP, Ridley AJ. Why three Rho proteins? RhoA, RhoB, RhoC, and cell motility. Exp Cell Res. 2004;301(1):43–9. doi: 10.1016/j.yexcr.2004.08.012.PubMedCrossRefGoogle Scholar
  47. 47.
    Pan Y, Bi F, Liu N, Xue Y, Yao X, Zheng Y, et al. Expression of seven main Rho family members in gastric carcinoma. Biochem Biophys Res Commun. 2004;315(3):686–91. doi: 10.1016/j.bbrc.2004.01.108.PubMedCrossRefGoogle Scholar
  48. 48.
    Yoo HY, Sung MK, Lee SH, Kim S, Lee H, Park S, et al. A recurrent inactivating mutation in RHOA GTPase in angioimmunoblastic T cell lymphoma. Nat Genet. 2014;46(4):371–5. doi: 10.1038/ng.2916.PubMedCrossRefGoogle Scholar
  49. 49.
    Sakata-Yanagimoto M, Enami T, Yoshida K, Shiraishi Y, Ishii R, Miyake Y, et al. Somatic RHOA mutation in angioimmunoblastic T cell lymphoma. Nat Genet. 2014;46(2):171–5. doi: 10.1038/ng.2872.PubMedCrossRefGoogle Scholar
  50. 50.
    Palomero T, Couronne L, Khiabanian H, Kim MY, Ambesi-Impiombato A, Perez-Garcia A, et al. Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas. Nat Genet. 2014;46(2):166–70. doi: 10.1038/ng.2873.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Nagarajan N, Bertrand D, Hillmer AM, Zang ZJ, Yao F, Jacques PE, et al. Whole-genome reconstruction and mutational signatures in gastric cancer. Genome Biol. 2012;13(12):R115. doi: 10.1186/gb-2012-13-12-r115.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Lochhead PA, Wickman G, Mezna M, Olson MF. Activating ROCK1 somatic mutations in human cancer. Oncogene. 2010;29(17):2591–8. doi: 10.1038/onc.2010.3.PubMedCrossRefGoogle Scholar
  53. 53.
    Clevers H, Nusse R. Wnt/β-catenin signaling and disease. Cell. 2012;149(6):1192–205. doi: 10.1016/j.cell.2012.05.012.PubMedCrossRefGoogle Scholar
  54. 54.
    Giles RH, van Es JH, Clevers H. Caught up in a Wnt storm: Wnt signaling in cancer. Biochim Biophys Acta. 2003;1653(1):1–24.PubMedGoogle Scholar
  55. 55.
    Wu J, Jiao Y, Dal Molin M, Maitra A, de Wilde RF, Wood LD, et al. Whole-exome sequencing of neoplastic cysts of the pancreas reveals recurrent mutations in components of ubiquitin-dependent pathways. Proc Nat Acad Sci USA. 2011;108(52):21188–93. doi: 10.1073/pnas.1118046108.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Jiang X, Hao HX, Growney JD, Woolfenden S, Bottiglio C, Ng N, et al. Inactivating mutations of RNF43 confer Wnt dependency in pancreatic ductal adenocarcinoma. Proc Nat Acad Sci USA. 2013;110(31):12649–54. doi: 10.1073/pnas.1307218110.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Ryland GL, Hunter SM, Doyle MA, Rowley SM, Christie M, Allan PE, et al. RNF43 is a tumour suppressor gene mutated in mucinous tumours of the ovary. J Pathol. 2013;229(3):469–76. doi: 10.1002/path.4134.PubMedCrossRefGoogle Scholar
  58. 58.
    Giannakis M, Hodis E, Jasmine Mu X, Yamauchi M, Rosenbluh J, Cibulskis K, et al. RNF43 is frequently mutated in colorectal and endometrial cancers. Nat Genet. 2014;46(12):1264–6. doi: 10.1038/ng.3127.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Sakamoto H, Kuboki Y, Hatori T, Yamamoto M, Sugiyama M, Shibata N, et al. Clinicopathological significance of somatic RNF43 mutation and aberrant expression of ring finger protein 43 in intraductal papillary mucinous neoplasms of the pancreas. Mod Pathol. 2015;28(2):261–7. doi: 10.1038/modpathol.2014.98.PubMedCrossRefGoogle Scholar
  60. 60.
    Koo B-K, Spit M, Jordens I, Low TY, Stange DE, van de Wetering M, et al. Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors. Nature. 2012;488(7413):665–9. doi: 10.1038/nature11308.PubMedCrossRefGoogle Scholar
  61. 61.
    Lin W, Kao HW, Robinson D, Kung HJ, Wu CW, Chen HC. Tyrosine kinases and gastric cancer. Oncogene. 2000;19(49):5680–9. doi: 10.1038/sj.onc.1203924.PubMedCrossRefGoogle Scholar
  62. 62.
    Lee JW, Soung YH, Seo SH, Kim SY, Park CH, Wang YP, et al. Somatic mutations of ERBB2 kinase domain in gastric, colorectal, and breast carcinomas. Clin Cancer Res. 2006;12(1):57–61. doi: 10.1158/1078-0432.ccr-05-0976.PubMedCrossRefGoogle Scholar
  63. 63.
    Moutinho C, Mateus AR, Milanezi F, Carneiro F, Seruca R, Suriano G. Epidermal growth factor receptor structural alterations in gastric cancer. BMC cancer. 2008;8:10. doi: 10.1186/1471-2407-8-10.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Liu Z, Liu L, Li M, Wang Z, Feng L, Zhang Q, et al. Epidermal growth factor receptor mutation in gastric cancer. Pathology. 2011;43(3):234–8. doi: 10.1097/PAT.0b013e328344e61b.PubMedCrossRefGoogle Scholar
  65. 65.
    Chmielecki J, Ross JS, Wang K, Frampton GM, Palmer GA, Ali SM, et al. Oncogenic alterations in ERBB2/HER2 represent potential therapeutic targets across tumors from diverse anatomic sites of origin. Oncologist. 2015;20(1):7–12. doi: 10.1634/theoncologist.2014-0234.PubMedCrossRefGoogle Scholar
  66. 66.
    Jaiswal BS, Kljavin NM, Stawiski EW, Chan E, Parikh C, Durinck S, et al. Oncogenic ERBB3 mutations in human cancers. Cancer Cell. 2013;23(5):603–17. doi: 10.1016/j.ccr.2013.04.012.PubMedCrossRefGoogle Scholar
  67. 67.
    Choi MR, An CH, Chung YJ, Choi YJ, Yoo NJ, Lee SH. Mutational and expressional analysis of ERBB3 gene in common solid cancers. APMIS. 2014;122(12):1207–12. doi: 10.1111/apm.12286.PubMedCrossRefGoogle Scholar
  68. 68.
    Prickett TD, Agrawal NS, Wei X, Yates KE, Lin JC, Wunderlich JR, et al. Analysis of the tyrosine kinome in melanoma reveals recurrent mutations in ERBB4. Nat Genet. 2009;41(10):1127–32. doi: 10.1038/ng.438.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Fassan M, Simbolo M, Bria E, Mafficini A, Pilotto S, Capelli P, et al. High-throughput mutation profiling identifies novel molecular dysregulation in high-grade intraepithelial neoplasia and early gastric cancers. Gastric Cancer. 2014;17(3):442–9. doi: 10.1007/s10120-013-0315-1.PubMedCrossRefGoogle Scholar
  70. 70.
    Jang JH, Shin KH, Park JG. Mutations in fibroblast growth factor receptor 2 and fibroblast growth factor receptor 3 genes associated with human gastric and colorectal cancers. Cancer Res. 2001;61(9):3541–3.PubMedGoogle Scholar
  71. 71.
    Vogelstein B, Kinzler KW. Cancer genes and the pathways they control. Nat Med. 2004;10(8):789–99. doi: 10.1038/nm1087.PubMedCrossRefGoogle Scholar
  72. 72.
    Zang ZJ, Ong CK, Cutcutache I, Yu W, Zhang SL, Huang D, et al. Genetic and structural variation in the gastric cancer kinome revealed through targeted deep sequencing. Cancer Res. 2011;71(1):29–39. doi: 10.1158/0008-5472.CAN-10-1749.PubMedCrossRefGoogle Scholar
  73. 73.
    Gaston D, Hansford S, Oliveira C, Nightingale M, Pinheiro H, Macgillivray C, et al. Germline mutations in MAP3K6 are associated with familial gastric cancer. PLoS Genet. 2014;10(10):e1004669. doi: 10.1371/journal.pgen.1004669.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Liang Q, Yao X, Tang S, Zhang J, Yau TO, Li X, et al. Integrative identification of Epstein-Barr virus-associated mutations and epigenetic alterations in gastric cancer. Gastroenterology. 2014;147(6):1350–62 e4. doi: 10.1053/j.gastro.2014.08.036.PubMedCrossRefGoogle Scholar
  75. 75.
    Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, et al. High frequency of mutations of the PIK3CA gene in human cancers. Science. 2004;304(5670):554. doi: 10.1126/science.1096502.PubMedCrossRefGoogle Scholar
  76. 76.
    Bader AG, Kang S, Vogt PK. Cancer-specific mutations in PIK3CA are oncogenic in vivo. Proc Natl Acad Sci USA. 2006;103(5):1475–9. doi: 10.1073/pnas.0510857103.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Janku F, Hong DS, Fu S, Piha-Paul SA, Naing A, Falchook GS, et al. Assessing PIK3CA and PTEN in early-phase trials with PI3K/AKT/mTOR inhibitors. Cell Rep. 2014;6(2):377–87. doi: 10.1016/j.celrep.2013.12.035.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of Oncology, Shanghai Medical CollegeFudan UniversityShanghaiChina
  2. 2.Tongji University Tianyou HospitalShanghaiChina
  3. 3.Department of Medical OncologyFudan University Shanghai Cancer CenterShanghaiChina

Personalised recommendations