Genes causing head and neck cancer
Cancer, including head and neck squamous cell carcinoma, arises by the accumulation of genetic and epigenetic changes in the DNA, leading to activation of oncogenes and inactivation of tumor suppressor genes and/or DNA stability genes. Recently, we showed that the progression of head and neck cancer can be summarized in four discrete steps that are of pathobiological and clinical importance:
- one or more genetic hits in a clonal unit in the mucosal epithelium lead to a so called "patch",
- by more subsequent hits a large precancerous lesion, a so called "field", develops,
- by further genetic progression the invasive carcinoma arises, and
- finally metastases develop.
Currently we are investigating the specific genetic alterations that are associated with these discrete steps, and aim to identify all the critical genes. The onset of genetic changes might be chemical carcinogens such as those in tobacco smoke, but also viral infection, and recently we showed that the human papillomavirus (HPV) plays a causative role in approximately 10% of the oral and oropharyngeal tumors. In addition, we generated an in vitro carcinogenesis model of mucosal keratinocytes. This model allows
- the analysis of putative cancer genes in relation to replicative lifespan and
- the screening for novel cancer genes using a functional genomics approach.
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- Sanne R. Martens-de Kemp, Remco Nagel, Marijke Stigter-van Walsum, et al. Functional Genetic Screens Identify Genes Essential for Tumor Cell; Survival in Head and Neck and Lung Cancer. Clin Cancer Res 2013;19:1994-2003 . Published OnlineFirst February 26, 2013