Abstract：
:A comprehensive description of genomic alterations in lung squamous cell carcinoma (lung SCC) has recently been reported, enabling the identification of genomic events that contribute to the oncogenesis of this disease. In lung SCC, one of the most frequently altered receptor tyrosine kinase families is the fibroblast growth factor receptor (FGFR) family, with amplification or mutation observed in all four family members. Here, we describe the oncogenic nature of mutations observed in FGFR2 and FGFR3, each of which are observed in 3% of samples, for a mutation rate of 6% across both genes. Using cell culture and xenograft models, we show that several of these mutations drive cellular transformation. Transformation can be reversed by small-molecule FGFR inhibitors currently being developed for clinical use. We also show that mutations in the extracellular domains of FGFR2 lead to constitutive FGFR dimerization. In addition, we report a patient with an FGFR2-mutated oral SCC who responded to the multitargeted tyrosine kinase inhibitor pazopanib. These findings provide new insights into driving oncogenic events in a subset of lung squamous cancers, and recommend future clinical studies with FGFR inhibitors in patients with lung and head and neck SCC.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Liao RG,Jung J,Tchaicha J,Wilkerson MD,Sivachenko A,Beauchamp EM,Liu Q,Pugh TJ,Pedamallu CS,Hayes DN,Gray NS,Getz G,Wong KK,Haddad RI,Meyerson M,Hammerman PSdoi
10.1158/0008-5472.CAN-12-3950subject
Has Abstractpub_date
2013-08-15 00:00:00pages
5195-205issue
16eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-12-3950journal_volume
73pub_type
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