Gene defects and mutant ALK kinase in human solid tumors

US8486645B2 · kind B2 · utility

Assignee

• CELL SIGNALING TECHNOLOGY, INC. · US

Inventors

• Klarisa Rikova · Reading, US
• Herbert Haack · Hamilton, US
• Laura Sullivan · Shrewsbury, US
• Ailan Guo · Lexington, US
• Anthony Possemato · Worcester, US
• Joan MacNeill · Litchfield, US
• Ting-Lei Gu · Woburn, US
• Jian Yu · New Providence, US

Key dates

• Filing date: Apr 3, 2012
• Grant date: Jul 16, 2013
• Expiry date: Apr 3, 2032

Classification

• Technology area (CPC Y): Emerging Cross-Sectional Technologies
• CPC primary: Y10T436/117497
• WIPO field: Measurement
• WIPO sector: Instruments

Abstract

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 polypeptides, probes for detecting it, isolated mutant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The invention also provides methods for determining the presence of these mutant 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.