Mutational and Functional Analysis of FANCB as a Candidate Gene for Sporadic Head and Neck Squamous Cell Carcinomas

Abstract

Abstract. Background Head and neck squamous cell carcinomas (HNSCCs) are the 6th most common type of cancers worldwide with varying rates in different ethnic populations (1-4). In the USA alone, over 60,000 new cases of HNSCCs are diagnosed and more than 13,000 patients die from HNSCCs each year (5). The tumor cells originate from the epithelium of the upper aerodigestive tract and undergo malignant transformation in a multistep process that is strongly influenced by an interplay between extrinsic (e.g. environmental or behavioral) and intrinsic (predominantly genetic) factors (1, 6). The four major cellular pathways implicated in the pathogenesis of HNSCCs are proliferation/survival, cell-cycle control, differentiation and adhesion/invasion signaling (7). The dysregulation of these pathways in the malignant cells is caused by somatic alterations/mutations in key genes such as TP53, HRAS, CCND1, NOTCH1 and others (7-9).The major behavioral risk factors for the development of HNSCCs are increased consumption of tobacco, and alcohol, but also infection with oncogenic human papilloma virus (HPV) (1, 2, 7). Several research groups including ours have established that a minority of patients with heterozygous germline mutations in known cancer susceptibility genes has an increased risk to develop HNSCC even in the absence of other behavioral risk

Identification by TCGA database search of five genes that are aberrantly expressed and involved in hepatocellular carcinoma potentially via DNA methylation changes

“…FANCB, one of the Fanconi anemia proteins, is involved in the repair of DNA lesions and its upregulation is suggested to be required for the survival of colon cancer [ 31 ]. FANCB is also reported to be associated with other types of cancers [ 32 , 33 ]. KIF family proteins, including KIF4A and KIF15 encode kinesin-related proteins which are molecular motor proteins that travel along microtubule tracks, play multiple roles in intracellular transport and cell division [ 34 ].…”

The signal transducer CD24 suppresses the germ cell program and promotes an ectodermal rather than mesodermal cell fate in embryonal carcinomas

“…One day prior transfection, 293T cells were seeded into 10 cm plates. For the transfection, 6 µg pczVSV-G plasmid [28], 6 µg of pCD/NL-BHΔ1 plasmid (Addgene #41791 [29]), and 6 µg of puc2CL6EGIP [30] or pLV-mCherry plasmid (Addgene #36084) were incubated in supplement-free DMEM. In parallel, a 45 µgÁµL À1 of polyethylenimine (PEI; Sigma-Aldrich, Taufkirchen, Germany) was added to supplement-free DMEM.…”