C-met mutations in lung cancer

A prognostic method comprising determining whether a lung cancer sample from a subject comprises a mutation in a nucleic acid sequence encoding human c-met, wherein the sequence is mutated in exon 14 and/or its flanking introns, wherein the mutation affects exon splicing.

A method of detecting lung cancer in a sample comprising determining whether the sample comprises a mutation in a nucleic acid sequence encoding human c-met, wherein the mutation results in an amino acid change at position N375, I638, V13, V923, I316 and/or E168.

A method of detecting lung cancer in a sample comprising determining whether the sample comprises a mutation in a nucleic acid sequence encoding human c-met, wherein the mutation is in exon 14 and/or its flanking introns, wherein the mutation affects exon splicing.

A method for distinguishing between non-cancerous and cancerous lung tissue, said method comprising determining whether a sample comprising the lung tissue comprises a mutation in a nucleic acid sequence encoding human c-met, wherein the mutation results in an amino acid change at position N375, I638, V13, V923, I316 and/or E168, wherein detection of the mutation in the sample is indicative of presence of cancerous lung tissue.

A method for distinguishing between non-cancerous and cancerous lung tissue, said method comprising determining whether a sample comprising the lung tissue comprises a mutation in a nucleic acid sequence encoding human c-met, wherein the mutation is in exon 14 and/or its flanking introns, wherein the mutation affects exon splicing, wherein detection of the mutation in the sample is indicative of presence of cancerous lung tissue.

A method of identifying a mutation in c-met in lung cancer, said method comprising contacting a lung cancer sample with an agent capable of detecting a mutation in a nucleic acid sequence encoding human c-met, wherein the mutation results in an amino acid change at position N375, I638, V13, V923, I316 and/or E168.

A method of identifying a mutation in c-met in lung cancer, said method comprising contacting a lung cancer sample with an agent capable of detecting a mutation in a nucleic acid sequence encoding human c-met, wherein the mutation is in exon 14 and/or its flanking introns, wherein the mutation affects exon splicing.

A method of identifying a lung cancer that is susceptible to treatment with a c-met inhibitor, said method comprising determining whether a lung cancer sample from a subject comprises a mutation in a nucleic acid sequence encoding human c-met, wherein the mutation results in an amino acid change at position N375, I638, V13, V923, I316 and/or E168.

A method of identifying a lung cancer that is susceptible to treatment with a c-met inhibitor, said method comprising determining whether a lung cancer sample from a subject comprises a mutation in a nucleic acid sequence encoding human c-met, whether the sequence is mutated in exon 14 and/or its flanking introns, wherein the mutation affects exon splicing.

A method of determining responsiveness of a lung cancer in a subject to treatment with a c-met inhibitor, said method comprising determining whether a lung cancer sample from a subject who has been treated with the c-met inhibitor comprises a mutation in a nucleic acid sequence encoding human c-met, wherein the mutation results in an amino acid change at position N375, I638, V13, V923, I316 and/or E168, wherein absence of the mutated nucleic acid sequence is indicative that the lung cancer is responsive to treatment with the c-met inhibitor.

A method of determining responsiveness of a lung cancer in a subject to treatment with a c-met inhibitor, said method comprising determining whether a lung cancer sample from a subject who has been treated with the c-met inhibitor comprises a mutation in a nucleic acid sequence encoding human c-met, whether the sequence is mutated in exon 14 and/or its flanking introns, wherein the mutation affects exon splicing, wherein absence of the mutated nucleic acid sequence is indicative that the lung cancer is responsive to treatment with the c-met inhibitor.

A method for monitoring minimal residual disease in a subject treated for lung cancer with a c-met inhibitor, said method comprising determining whether a sample from a subject who is treated with the c-met inhibitor comprises a mutation in a nucleic acid sequence encoding human c-met, wherein the mutation results in an amino acid change at position N375, I638, V13, V923, I316 and/or E168, wherein detection of said mutation is indicative of presence of minimal residual lung cancer.

A method for monitoring minimal residual disease in a subject treated for lung cancer with a c-met inhibitor, said method comprising determining whether a lung cancer sample from a subject who has been treated with the c-met inhibitor comprises a mutation in a nucleic acid sequence encoding human c-met, whether the sequence is mutated in exon 14 and/or its flanking introns, wherein the mutation affects exon splicing, wherein detection of said mutation is indicative of presence of minimal residual lung cancer.

A method for amplification of a nucleic acid encoding human c-met, wherein the nucleic acid comprises a mutation that results in an amino acid change at position N375, I638, V13, V923, I316 and/or E168 relative to wild type c-met, said method comprising amplifying a sample suspected or known to comprise the nucleic acid with a nucleic acid comprising the sequence of any of the primers/probes listed in Table S4 in FIG. 7.

A method for amplification of a nucleic acid encoding human c-met, wherein the nucleic acid comprises a mutation in exon 14 and/or its flanking introns, wherein the mutation affects exon splicing, said method comprising amplifying a sample suspected or known to comprise the nucleic acid with a nucleic acid comprising the sequence of any of the primers/probes listed in Table S4 in FIG. 7.

A method for identifying a specific mutation in c-met in a sample, wherein the mutation is one that results in an amino acid change at position N375, I638, V13, V923, I316 and/or E168 relative to wild type c-met, said method comprising contacting the sample with a nucleic acid comprising the sequence of any of the primers/probes listed in Table S4 in FIG. 7.

A method for identifying a specific mutation in c-met in a sample, wherein the mutation is in exon 14 and/or its flanking introns, wherein the mutation affects exon splicing, said method comprising contacting the sample with a nucleic acid comprising the sequence of any of the primers/probes listed in Table S4 in FIG. 7.

A method of detecting presence of a mutated c-met in lung cancer, the method comprising contacting a sample suspected or known to comprise mutated c-met with a nucleic acid comprising the sequence of any of the primers/probes listed in Table S4 in FIG. 7.

A method of detecting presence of a mutated c-met in lung cancer, the method comprising contacting a sample suspected or known to comprise mutated c-met with an antigen binding agent, wherein binding or lack thereof, of the agent is indicative of presence or absence of a c-met polypeptide comprising a deletion of at least a portion of exon 14.

A method for detecting a cancerous disease state in a lung tissue, said method comprising determining whether a sample from a subject suspected of having lung cancer comprises a mutation in a nucleic acid sequence encoding human c-met, wherein the mutation results in an amino acid change at position N375, I638, V13, V923, I316 and/or E168, wherein detection of said mutation is indicative of presence of a cancerous disease state in the lung of the subject.

A method for detecting a cancerous disease state in a lung tissue, said method comprising determining whether a sample from a subject suspected of having lung cancer comprises a mutation in a nucleic acid sequence encoding human c-met, whether the sequence is mutated in exon 14 and/or its flanking introns, wherein the mutation affects exon splicing, wherein detection of said mutation is indicative of presence of minimal residual lung cancer.

The method of any of the preceding claims in which a mutation affects exon splicing, wherein the mutation affects exon splicing such that a c-met protein is produced that lacks at least a portion of exon 14.

The method of any of the preceding claims in which a mutation affects exon splicing, wherein the mutation comprises a mutation indicated in FIG. 6 (Table S3).

A lung cancer biomarker, wherein the biomarker comprises c-met comprising a mutation that results in an amino acid change at position N375, I638, V13, V923, I316 and/or E168.

A lung cancer biomarker, wherein the biomarker comprises c-met comprising a mutation in exon 14 and/or its flanking introns, wherein the mutation affects exon splicing.

A lung cancer imaging agent, wherein the agent specifically binds c-met comprising a mutation, wherein the agent binds a c-met polypeptide comprising a mutation at position N375, I638, V13, V923, I316 and/or E168 of the protein, or wherein the agent binds a c-met encoding nucleic acid comprising a mutation at a nucleic acid position corresponding to a change in amino acid at position N375, I638, V13, V923, I316 and/or E168.

A lung cancer imaging agent, wherein the agent specifically binds c-met polypeptide comprising a deletion of at least a portion of exon 14, or wherein the agent specifically binds c-met encoding nucleic acid that lacks at least a portion of the sequence that encodes exon 14.

A polynucleotide capable of specifically hybridizing to c-met encoding nucleic acid comprising a mutation at a nucleic acid position corresponding to a change in amino acid at position N375, I638, V13, V923, I316 and/or E168.

A polynucleotide capable of specifically hybridizing to c-met encoding nucleic acid that lacks at least a portion of the sequence that encodes exon 14.

An antigen binding agent capable of specifically binding to a c-met polypeptide comprising a mutation at position N375, I638, V13, V923, I316 and/or E168.

An antigen binding agent capable of specifically binding to a c-met polypeptide comprising a deletion of at least a portion of exon 14.

An array/gene chip/gene set comprising polynucleotides capable of specifically hybridizing to c-met encoding nucleic acid comprising a mutation at a nucleic acid position corresponding to a change in amino acid at position N375, I638, V13, V923, I316 and/or E168.

An array/gene chip/gene set comprising polynucleotides capable of specifically hybridizing to c-met encoding nucleic acid that lacks at least a portion of the sequence that encodes exon 14.

A computer-readable medium comprising human c-met amino acid polypeptide sequence comprising a mutation at position N375, I638, V13, V923, I316 and/or E168, and/or nucleic acid sequence encoding a human c-met polypeptide comprising a mutation at a nucleic acid position corresponding to a change in amino acid at position N375, I638, V13, V923, I316 and/or E168.

A computer-readable medium comprising human c-met amino acid polypeptide sequence comprising a deletion of at least a portion of exon 14, and/or human c-met encoding nucleic acid that lacks at least a portion of the sequence that encodes exon 14.

A kit comprising a composition of the invention, and instructions for using the composition to detect mutation in human c-met at position N375, I638, V13, V923, I316 and/or E168.

A kit comprising a composition of the invention, and instructions for using the composition to detect human c-met comprising a deletion of exon 14.