In accordance with the invention,
novel gene deletions and translocations involving
chromosome 2 resulting in fusion proteins combining part of
Anaplastic Lymphoma Kinase (ALK)
kinase with part of a secondary
protein have now been identified in human
solid tumors, e.g. non-
small cell lung carcinoma (NSCLC). Secondary proteins include
Echinoderm Microtubule-Associated
Protein-Like 4 (EML-4) and TRK-
Fusion Gene (TFG). The EML4-ALK
fusion protein, which retains ALK
tyrosine kinase activity, was confirmed to drive the proliferation and survival of NSCLC characterized by this
mutation. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed
mutant ALK
kinase polypeptides, probes for detecting it, isolated
mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of this new
fusion protein enables new methods for determining the presence of these
mutant ALK kinase polypeptides in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a
cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.