Using next-generation whole-exome sequencing approaches to elucidate the genetic basis for nasopharyngeal carcinoma

Abstract

Nasopharyngeal carcinoma (NPC) is an intriguing cancer with a high prevalence in Southern Chinese, but is rare in most other parts of the world. In Hong Kong, where this cancer is endemic, NPC is ranked as one of the top cancers in incidence. Its peak age at diagnosis is in the upper 40’s. However, there are patients who develop this cancer at a very early age. Genetic susceptibility to NPC is further indicated by familial clustering, as occurs in at least 10% of the endemic population in Hong Kong. Early-age onset (EAO) and family history-positive (FH+) NPC patients were recruited into this study from Hong Kong and other endemic regions of Southern China, and over seven hundred non-cancerous individuals were included as controls. Whole-exome sequencing (WES) approach was utilized as an unbiased genome-wide screen to identify genes associated with NPC risk in these populations. We hypothesized that these two groups of NPC patients may harbor aberrations in genes associated with chromosomal instability and DNA repair that contribute to the genetic risk of an individual to develop this cancer. Using such an approach, we identified several altered genes in the DNA damage and repair pathways and involved in chromosomal instability in these NPC patients. The results from discovery phase are still being validated by targeted next-generation sequencing in an independent patient cohort and a summary of findings related to genomic instability will be presented.