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.

口腔鳞状细胞癌（OSCC）是头颈部鳞状细胞癌（HNSCC）的常见亚型，但家族性OSCC的发病机制尚不清楚。在这里，我们分析了口腔癌常染色体显性表达家族的全基因组序列，并确定原癌基因VAV2和IQGAP1是导致该家族口腔癌的主要因素。这两个基因在偶发的OSCC和HNSCC中也经常发生突变。功能分析表明，有害的变异体靶向与肿瘤发生相关的途径，因此证实了这些新颖的遗传变异体有助于建立家族性OSCC的易感性。