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

• Published in: Cell discovery Vol. 5; no. 1; pp. 1 - 9
• Main Authors: Huang, Yaping, Zhao, Jizhi, Mao, Guogen, Lee, Grace Sanghee, Zhang, Jia, Bi, Lijun, Gu, Liya, Chang, Zhijie, Valentino, Joseph, Li, Guo-Min
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26-11-2019; Springer Nature B.V
• Subjects: 631/67/1665; 631/67/395; 631/67/68; Biomedical and Life Sciences; Cell Biology; Cell Culture; Cell Cycle Analysis; Cell Physiology; Genetic diversity; Genomes; Head & neck cancer; IQGAP1 protein; Life Sciences; Neck; Oral cancer; Oral carcinoma; Oral squamous cell carcinoma; Proto-oncogenes; Squamous cell carcinoma; Stem Cells; Tumorigenesis
• ISSN: 2056-5968; 2056-5968
• DOI: 10.1038/s41421-019-0126-6

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.