Identification of a Novel Fusion Gene (HLA-E and HLA-B) by RNA-seq Analysis in Esophageal Squamous Cell Carcinoma

  • Jiang, Yu-Zhang (Department of Medical Laboratory, Huai'an First People's Hospital, Nanjing Medical) ;
  • Li, Qian-Hui (Department of Medical Laboratory, Huai'an First People's Hospital, Nanjing Medical) ;
  • Zhao, Jian-Qiang (Department of Cardiothoracic Surgery, Huai'an First People's Hospital, Nanjing Medical) ;
  • Lv, Jun-Ji (Department of Cardiothoracic Surgery, Huai'an First People's Hospital, Nanjing Medical)
  • 발행 : 2014.03.01


Esophageal squamous cell carcinoma (ESCC) is the most common histologic subtype of esophageal cancer and is characterized by a poor prognosis. Determining gene changes in ESCCs should improve understanding of putative risk factors and provide potential targets for therapy. We sequenced about 55 million pair-end reads from a pair of adjacent normal and ESCC samples to identify the gene expression level and gene fusion. Sanger sequencing was used to verify the result. About 17 thousand genes were expressed in the tissues, of which approximately 2400 demonstrated significant differences between tumor and adjacent non tumor tissue. GO and KEGG pathway analysis revealed that many of these genes were associated with cellular adherence and movement, simulation responses and immune responses. Notably we identified and validated one fusion gene, HLA-E and HLA-B, located 1 MB apart. We also identified thousands of remarkably expressed transcripts. In conclusion, a novel fusion gene HLA-E and HLA-B was identified in ESCC via whole transcriptome sequencing, which would be a biomarker for ESCC diagnosis and target for therapy, shedding new light for better understanding of ESCC tumorigenesis.


  1. Bandla S, Pennathur A, Luketich JD, et al (2012). Comparative genomics of esophageal adenocarcinoma and squamous cell carcinoma. Ann Thorac Surg, 93, 1101-6.
  2. de Kruijf EM, Sajet A, van Nes JG, et al (2010). HLA-E and HLA-G expression in classical HLA class I-negative tumors is of prognostic value for clinical outcome of early breast cancer patients. J Immunol, 185, 7452-9.
  3. Futreal PA, Coin L, Marshall M, et al (2004). A census of human cancer genes. Nat Rev Cancer, 4, 177-83.
  4. Gibb EA, Enfield KS, Tsui IF, et al (2011). Deciphering squamous cell carcinoma using multidimensional genomic approaches. J Skin Cancer, 2011, 541405.
  5. Hanahan D, Weinberg RA (2011). Hallmarks of cancer: the next generation. Cell, 144, 646-74.
  6. Huang da W, Sherman BT, Lempicki RA (2009). Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc, 4, 44-57.
  7. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90.
  8. Ju YS, Lee WC, Shin JY, et al (2012). A transforming KIF5B and RET gene fusion in lung adenocarcinoma revealed from whole-genome and transcriptome sequencing. Genome Res, 22, 436-45.
  9. Kim D, Salzberg SL (2011). TopHat-Fusion: an algorithm for discovery of novel fusion transcripts. Genome Biol, 12, R72.
  10. Kren L, Slaby O, Muckova K, et al (2011). Expression of immune-modulatory molecules HLA-G and HLA-E by tumor cells in glioblastomas: an unexpected prognostic significance? Neuropathology, 31, 129-34.
  11. Langmead B, Trapnell C, Pop M, Salzberg SL (2009). Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol, 10, R25.
  12. Le YS, Kim TE, Kim BK, et al (2002). Alterations of HLA class I and class II antigen expressions in borderline, invasive and metastatic ovarian cancers. Exp Mol Med, 34, 18-26.
  13. Lin Y, Totsuka Y, He Y, et al (2013). Epidemiology of esophageal cancer in Japan and China. J Epidemiol, 23, 233-42.
  14. Luo A, Kong J, Hu G, et al (2004). Discovery of Ca2+-relevant and differentiation-associated genes downregulated in esophageal squamous cell carcinoma using cDNA microarray. Oncogene, 23, 1291-9.
  15. Ma S, Bao JY, Kwan PS, et al (2012). Identification of PTK6, via RNA sequencing analysis, as a suppressor of esophageal squamous cell carcinoma. Gastroenterology, 143, 675-86 e1-12.
  16. Maher CA, Kumar-Sinha C, Cao X, et al (2009). Transcriptome sequencing to detect gene fusions in cancer. Nature, 458, 97-101.
  17. Marin R, Ruiz-Cabello F, Pedrinaci S, et al (2003). Analysis of HLA-E expression in human tumors. Immunogenetics, 54, 767-75.
  18. Ren S, Peng Z, Mao JH, et al (2012). RNA-seq analysis of prostate cancer in the Chinese population identifies recurrent gene fusions, cancer-associated long noncoding RNAs and aberrant alternative splicings. Cell Res, 22, 806-21.
  19. Spaans VM, Peters AA, Fleuren GJ, Jordanova ES (2012). HLA-E expression in cervical adenocarcinomas: association with improved long-term survival. J Transl Med, 10, 184.
  20. Trapnell C, Pachter L, Salzberg SL (2009). TopHat: discovering splice junctions with RNA-Seq. Bioinformatics, 25, 1105-11.
  21. Trapnell C, Williams BA, Pertea G, et al (2010). Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat Biotechnol, 28, 511-5.
  22. Wang Z, Gerstein M, Snyder M (2009). RNA-Seq: a revolutionary tool for transcriptomics. Nat Rev Genet, 10, 57-63.
  23. Zhang Q, Zhang J, Jin H, Sheng S (2013). Whole transcriptome sequencing identifies tumor-specific mutations in human oral squamous cell carcinoma. BMC Med Genomics, 6, 28.

피인용 문헌

  1. Oesophageal squamous cell carcinoma (ESCC): Advances through omics technologies, towards ESCC salivaomics vol.9, pp.4, 2015,
  2. Chronic sun exposure-related fusion oncogenes EGFR-PPARGC1A in cutaneous squamous cell carcinoma vol.7, pp.1, 2017,
  3. High expression of HLA-DQA1 predicts poor outcome in patients with esophageal squamous cell carcinoma in Northern China vol.98, pp.8, 2019,