Molecular Genetics of Nasopharyngeal Carcinoma

Abstract

Nasopharyngeal carcinoma (NPC) is a distinctive type of squamous cell carcinoma of the head and neck region with remarkable ethnic and geographic distribution. It is consistently associated with Epstein–Barr virus (EBV) infection and serves as a fascinating model to understand the complex interaction among environmental, viral, and genetic factors in human tumourigenesis. The development of NPC involves clonal expansion of EBV‐infected cells and cumulative genetic and epigenetic changes. Both viral and cellular genes contribute to disease pathogenesis and their interplay creates distinct phenotypes, unique molecular features and tumour microenvironment. Recent findings on EBV‐encoded and cellular miRNAs demonstrate their importance in NPC progression by altering multiple cellular pathways. On the basis of current knowledge, we proposed a stepwise model describing the initiation events and the role of EBV latent infection and multiple genetic changes in NPC tumourigenesis.

Key Concepts:

  • Nonkeratinising NPC is consistently associated with EBV infection.

  • The development of NPC involves EBV latent infection and cumulative genetic and epigenetic changes influenced by predisposing genetic factors and environmental carcinogens.

  • Inactivation of tumour suppressor genes at chromosomes 3p and 9p and clonal expansion of EBV‐infected cells are critical initiation events in NPC tumourigenesis.

  • EBV‐encoded and cellular miRNAs contribute to the NPC progression by altering multiple cellular pathways and modulating EBV latent gene expression.

  • The interplay between viral and cellular genes contributes to the establishment of distinct phenotypes, unique molecular features and tumour microenvironment of NPC.

Keywords: nasopharyngeal carcinoma; Epstein–Barr virus; tumour suppressor gene; oncogene; DNA methylation; miRNA; multistep tumourigenesis

Figure 1.

Model of the progression of NPC tumourigenes is driven by EBV infection and multiple genetic changes.

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Further Reading

Gourzones C, Barjon C and Busson P (2012) Host‐tumor interactions in nasopharyngeal carcinomas. Seminars in Cancer Biology 22(2): 127–136.

Kaneda A, Matsusaka K, Aburatani H and Fukayama M (2012) Epstein‐Barr virus infection as an epigenetic driver of tumorigenesis. Cancer Research 72(14): 3445–3450.

Lee AW, Lin JC and Ng WT (2012) Current management of nasopharyngeal cancer. Seminars in Radiation Oncology 22(3): 233–244.

Lo AK, Dawson CW, Jin DY and Lo KW (2012) The pathological roles of BART miRNAs in nasopharyngeal carcinoma. Journal of Pathology 227(4): 392–403.

Lo KW, To KF and Huang DP (2004) Focus on nasopharyngeal carcinoma. Cancer Cell 5(5): 423–428.

Tsao SW, Tsang CM, Pang PS et al. (2012) The Biology of EBV infection in human epithelial cells. Seminars in Cancer Biology 22(2): 137–143.

Young LS and Rickinson AB (2004) Epstein–Barr virus: 40 years on. Nature Reviews Cancer 4(10): 757–768.

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Lun, Samantha Wei‐Man, Cheung, Chartia Ching‐Mei, Chow, Chit, Chung, Grace Tin‐Yun, and Lo, Kwok‐Wai(Sep 2013) Molecular Genetics of Nasopharyngeal Carcinoma. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0024927]