Table 1.

Non-chemically induced transgenic mice models of oral cavity cancers (OCC)

Pathway/ Gene family	Gene	Function	Freq. in NGS	Epithelial mouse model genotype	Tumour type	Reference
p53 family	TP53	Tumour suppressor involved in apoptosis, activates DNA repair proteins, cell cycle regulation at G1/S checkpoint	50 - 78%	p53-/- or mutant p53 mice with chemical carcinogens or mutant KRAS	Various HNSCC	Acin, Raimondi [35,36]
	TP63	Involved in development and regulation of apoptosis	8%	Not described	-	n/a
Nesprins	SYNE1,2	Found in the outer nuclear membrane and bind to actin filaments	24%	Not described	-	n/a
Notch	NOTCH1,2,3	Transmembrane proteins that are involved in development by controlling cell fate decisions by regulating interactions between adjacent cells.	22%	NOTCH1-/-	Basel Cell Carcinoma	Nicolas [74], Agrawal [21]
HPV Oncogenes	E6	Degrades p53 through ubiquitination	15%	HPV-E6/E7 with chemical carcinogens or mutant Hras	Papillomas of the lip	Schreiber [51]
	E7	Binds pRb to free the transcription factor E2F
PI3K/AKT/mTOR	PIK3CA	Oncogene	8%	Not described	-	n/a
	PTEN	Tumor suppressor that regulates AKT	8%	myrAKT PTEN-/-	Dysplastic lesions in the palate, cheeks, and lips	Bian, Moral [80,82]
TGF-β pathway	TGF-β	Regulates proliferation and differentiation, angiogenesis, and serves as an immune modulator	Not described	TGFBR1-/-	OCC, ears, periorbital, perianal	Bian [81]
	SMAD4	Downstream transcription factor that activates apoptosis	Not described	SMAD4-/-	OCC, lymph node mets	Bornstein [83]
	TGFB2	Encodes transmembrane Ser/Thr protein kinase that is activated by TGF-β, amongst other signalling molecules	Not described	Not described	-	Lu [82]
RAS/RAF/ MEK/MAPK	RASSF1A	Tumour suppressor involved in DNA repair and cell cycle arrest; negative regulator of RAS	Not described	G12D mutant KRAS	Benign squamous papillomas of oral mucosa, tongue and palate	Caulin [67]
	EGFR	Epidermal growth factor receptor; downstream mediator of RAS	Not described	Not described	-	n/a
Cyclins	Cyclin D1	Promotes cellular proliferation by enabling cells to enter S phase and synthesize DNA in preparation for cell division	Not described	L2-CyclinD1	Hyperplasia of tongue, oesophagus	Mueller [76], Nakagawa [77]
Pocket protein family	RB1	Tumour suppressor that inhibits cell cycle (G1/S) and is involved in chromatin remodelling	3%	pRb/p107-deficient pRB/p130-deficient	Head and neck Squamous cell carcinomas	Shin [56]
	RBL1	Gene product p107 is a tumour suppressor involved in cell cycle regulation		pRb/p107-deficient	Head and neck Squamous cell carcinomas	Shin [56]
	NOLC1	Gene product is p130, unclear function		pRb/p130-deficient	Head and neck Squamous cell carcinomas	Shin [56]
Interferon regulator transcription factor family	IRF6	Involved in the formation of connective tissues	Not described	Not described	-	n/a
F-box protein family	FBXW7	Binds to cyclin E and targets it for ubiquitination to prevent progression from G1 to S phase	Not described	Not described	-	n/a
	RIPK4	Serine/threonine protein kinase that interacts with PKC-δ and can also activate NFkappaB.	3%	Not described	-	n/a
	DICER1	RNA helicase that functions as a ribonuclease in RNA interference and microRNA pathways to repress gene expression	3%	Not described	-	n/a

NGS = next generation sequencing.