Consistent with overexpression of a H3K36me2-specific demethylase KDM2B in T-cell and B-cell acute lymphoblastic leukemia and in acute myeloid leukemia, we found its overexpression in almost all hematopoietic cell lines

Research Institute. The corresponding author is the Director of the Ohlson Research Initiative. This does not alter our adherence to all the PLoS ONE policies on sharing data and materials, as detailed online in the guide for authors. E-mail: [email protected]. These authors contributed equally to this work. Introduction main, and an intracellular tyrosine kinase domain. EGFR mediates a variety of responses including growth, proliferation, angiogenesis and metastasis. On ligand binding, EGFR can activate two major signalling pathways: Ras/MAPK and PI3K/ AKT/mTOR pathways. EGFR is ubiquitously expressed in normal epithelial tissue but is over-expressed in several cancers including lung, glioblastoma, prostrate, breast, colon, ovary and head and neck. Mutations in the EGFR gene have also been described in a variety of cancers. Our study focuses on the most common and well-characterized EGFR mutant, EGFR class III variant . EGFRvIII is February 2012 | Volume 7 | Issue 2 | e31723 EGFRvIII Expression in Oral Cancer a cancer-specific deletion of exons 2 to 7 that results in a truncated extracellular domain of EGFR. The corresponding deletion of amino acids 30297 within the extracellular ligandbinding domain, results in a ligand-independent form of EGFR with constitutive tyrosine kinase activity, leading to increased cell proliferation and inhibition of apoptosis. EGFRvIII expression is frequently associated with amplification and overexpression of GSK-516 wild-type EGFR and EGFRvIII-expressing tumors are more resistant to radiotherapy and chemotherapy. The EGFRvIII mutant was first detected in glioblastomas and approximately 30% of glioblastomas express EGFRvIII. EGFRvIII has been reported in lung squamous cell carcinomas but not in adenocarcinomas. EGFRvIII has also been reported in breast cancer and ovarian cancer. In prostrate tumors, EGFRvIII expression increases progressively during the transition from pre-malignant prostate lesions to the malignant phenotype. Previous reports suggest that EGFR is “ 21526763 over-expressed in,90% of head and neck squamous cell carcinoma and EGFR over-expression has been linked to the presence of EGFRvIII at other cancer sites. Therefore, recent studies have examined the role of EGFRvIII in HNSCC etiology. However, the frequency of EGFRvIII in head and neck cancer is disputed. Two studies have reported the presence of EGFRvIII in 42% of HNSCC patients but another group did not detect any EGFRvIII in HNSCC patients. One study, specifically in laryngeal carcinoma patients, reported the presence of EGFRvIII in,15% of tumor samples. The level of EGFR protein expression in HNSCC can vary according to the specific subsite; for instance, carcinomas of the pharynx and oral cavity tend to have higher EGFR expression than those of the larynx. Therefore, the frequency of EGFRvIII expression may also differ in distinct HNSCC subsites. Despite the lack of consensus on the frequency of EGFRvIII in HNSCC, only one study has discussed the frequency of EGFRvIII in specific HNSCC subsites which include malignancies of the oral cavity, pharynx and larynx. Oral squamous cell carcinoma accounts for approximately 30% of all HNSCCs. The 5-year survival rate for OSCC is approximately 50% and has changed little in the last few decades. This failure of conventional therapies supports the use of novel therapeutic strategies in OSCC. Therapeutic agents that target specific abnormalities in HNSCC have been employed successfully in recent years. The red