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

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

doi:10.1038/s41421-019-0126-6

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

Cell Discov. 2019 Nov 26:5:57. doi: 10.1038/s41421-019-0126-6. eCollection 2019.

Authors

Yaping Huang^#¹, Jizhi Zhao^#², Guogen Mao³, Grace Sanghee Lee³, Jia Zhang⁴, Lijun Bi⁴, Liya Gu¹, Zhijie Chang⁵, Joseph Valentino⁶, Guo-Min Li^{1

3}

Affiliations

¹ 1Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390 USA.
² 4Department of Stomatology, Peking Union Medical College Hospital, Beijing, 100730 China.
³ 2Department of Toxicology and Cancer Biology, University of Kentucky College of Medicine, Lexington, KY 40536 USA.
⁴ 5Insititute of Biophysics, Chinese Academy of Sciences, Beijing, 100101 China.
⁵ 6Department of Basic Medical Sciences, Tsinghua University School of Medicine, Beijing, 100084 China.
⁶ 3Department of Otolaryngology, Head & Neck Surgery, University of Kentucky College of Medicine, Lexington, KY 40536 USA.

^# Contributed equally.

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.

Keywords: Cancer genetics; Oncogenes; Oral cancer.