Identification of novel genetic variants predisposing to familial oral squamous cell carcinomas

Yaping Huang,Liya Gu,Guo-Min Li,Lijun Bi,Jizhi Zhao,Zhijie Chang,Joseph Valentino,Jia Zhang,Guogen Mao,Grace Sanghee Lee

doi:10.1038/s41421-019-0126-6

Abstract

Oral squamous cell carcinoma (OSCC) is a common subtype of head and neck squamous cell carcinoma (HNSCC), but the pathogenesis underlying familial OSCCs is unknown. Here, we analyzed whole-genome sequences of a family with autosomal dominant expression of oral tongue cancer and identified proto-oncogenes VAV2 and IQGAP1 as the primary factors responsible for oral cancer in the family. These two genes are also frequently mutated in sporadic OSCCs and HNSCCs. Functional analysis revealed that the detrimental variants target tumorigenesis-associated pathways, thus confirming that these novel genetic variants help to establish a predisposition to familial OSCC.

Highlights

Oral squamous cell carcinoma (OSCC) is one of the most common cancer types worldwide and occurs frequently in Western countries[1,2]
When we compared with sequencing data from the three non-OSCC cell lines, HeLa, SF188, and KNS42, we found that only mutations in VAV2 and IQGAP1 genes seemed to be specific to oral cancers, as all three non-oral cancer lines displayed mutations in the other genes, but not in VAV2 and IQGAP1
The results revealed that the mutation frequencies of both VAV2 and IQGAP1 are higher in head and neck squamous cell carcinoma (HNSCC) than in any other cancer types (Fig. 3)

Summary

Introduction

Oral squamous cell carcinoma (OSCC) is one of the most common cancer types worldwide and occurs frequently in Western countries[1,2]. In the United States, more than 50,000 OSCC cases were diagnosed in 2018, with more than 10,000 deaths. Tobacco use and alcohol consumption are considered the major risk factors for OSCCs3–5. Human papillomavirus (HPV) is another risk factor[6,7]. OSCCs occur sporadically in populations, epidemiological studies have suggested hereditary risks for OSCCs8,9. The hereditary factors that predispose to OSCCs are largely unknown

Methods

Results

Conclusion