| 摘要 |
The invention provides the identification of the presence of polypeptides with ALK kinase activity in human cancer, such as ovarian cancer. In some embodiments, the polypeptide with ALK kinase activity is the result of a fusion between an ALK-encoding polynucleotide and an FN1 -encoding polynucleotide. Six different fusion polypeptides are described, three that include the transmembrane and kinase domains of ALK fused to the extracellular domain of the FN1 protein, and three that include the kinase domain (but not the transmembrane domain) of ALK fused to the extracellular domain of the FN1 protein. The invention also provides the discovery of full length ALK expression in ovarian cancer. In some embodiments, this aberrant expression of full length ALK in ovarian cancer results from an amplified ALK gene copy number in the ovarian cancer. The invention, in part, also provides a truncated ALK polypeptide which contains the transmembrane and the kinase domains of ALK but lacks the extracellular domain of ALK protein. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed polypeptides (e.g., a FN1-ALKvariantl fusion polypeptide), probes for detecting the polynucleotides, isolated polypeptides, recombinant polypeptides, and reagents for detecting the polypeptides and polynucleotides. In some embodiments, the invention enables new methods for determining the presence of a polypeptide with ALK kinase activity in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer (e.g., an ovarian cancer). |
