Nasopharyngeal Cancer: Molecular Landscape

Abstract

Nasopharyngeal carcinoma (NPC) is a unique epithelial malignancy arising from the superior aspect of the pharyngeal mucosal space, associated with latent Epstein-Barr virus infection in most cases. The capacity to characterize cancer genomes in unprecedented detail is now providing insights into the genesis and molecular underpinnings of this disease. Herein, we provide an overview of the molecular aberrations that likely drive nasopharyngeal tumor development and progression. The contributions of major Epstein-Barr virus-encoded factors, including proteins, small RNAs, and microRNAs, along with their interactions with pathways regulating cell proliferation and survival are highlighted. We review recent analyses that clearly define the role of genetic and epigenetic variations affecting the human genome in NPC. These findings point to the impact of DNA methylation and histone modifications on gene expression programs that promote this malignancy. The molecular interactions that allow NPC cells to evade immune recognition and elimination, which is crucial for the survival of cells expressing potentially immunogenic viral proteins, are also described. Finally, the potential utility of detecting host and viral factors for the diagnosis and prognosis of NPC is discussed. Altogether, the studies summarized herein have greatly expanded our knowledge of the molecular biology of NPC, yet much remains to be uncovered. Emerging techniques for using and analyzing well-annotated biospecimens from patients with NPC will ultimately lead to a greater level of understanding, and enable improvements in precision therapies and clinical outcomes.

Genomic Analysis of Nasopharyngeal Carcinoma Reveals TME-Based Subtypes

“…However, prior work has identified several recurrent genomic alterations in NPC, including deletion of the p16-locus on cytoband 9p21, CCND1 amplification, TP53 mutation, inactivating mutations in negative regulators of the NF-kB pathway, mutations in MAPK and PI3K signaling pathways, and mutations in epigenetic regulators like MLL3 (18,19,21). In this study, we extend this prior work by presenting an integrated analysis of RNA sequencing (RNA-seq), whole-exome sequencing, copy number analysis, histology, and clinical data for 113 patients with undifferentiated NPC to characterize the disease at a molecular level.…”

Whole-exome sequencing identifies multiple loss-of-function mutations of NF-κB pathway regulators in nasopharyngeal carcinoma

“…Previous studies suggest that the loss of chromosomes 3p and 9p regions is an early event for the transformation of the normal nasopharyngeal epithelium (2). The copy number losses in chromosomes 11q, 13q, 14q, and 16q and copy number gains in 11q and 12p are also frequently reported (1). Moreover, methylome studies of clinical samples reveal widespread methylation changes in NPC tumors (3).…”

“…The predominant WHO subtype of NPC in Asia is nonkeratinizing undifferentiated NPC. One critical etiological factor for NPC is EBV infection, marking it as one of the most important human virus-associated cancers (1). It is well-accepted that host genetics, EBV infection, and environmental factors together contribute to the pathogenesis of NPC.…”

“…NPC is a unique cancer that arises after the accumulation of a number of critical genetic and epigenetic events that contribute to tumor development (1). Previous studies suggest that the loss of chromosomes 3p and 9p regions is an early event for the transformation of the normal nasopharyngeal epithelium (2).…”

Functions and Roles of Long-Non-Coding RNAs in Human Nasopharyngeal Carcinoma

“…In contrast to patients with early-stage NPC, who have 5-year overall survival (OS) rate for up to 95% [5-7], the 5-year OS rate declines to 41%–63% in patients with advanced-stage disease [8, 9]. Genetic predisposition, and epigenetic variations, ethnic background, environmental factors including exposure to chemical carcinogens, and latent Epstein-Barr virus (EBV) infection, among others play important roles in the development of this malignancy [10-13]. According to global cancer statistics reported by the International Agency for Research on Cancer, over 85, 000 new NPC cases occur annually, among which 80 % are located in Asia and 5 % in Europe [14].…”