Methods of diagnosing and prognosing lung cancer

Abstract

The present invention provides methods of detecting cancer using biomarkers.

1 . A method for determining the aggressiveness of a lung cancer in a mammal, said method comprising determining, in a test sample from said mammal, the presence or absence of Lkb1 and correlating said presence or absence with said aggressiveness. 
     
     
         2 . The method of  claim 1 , wherein said mammal is a human. 
     
     
         3 . The method of  claim 1 , wherein said test sample is a tumor biopsy. 
     
     
         4 . The method of  claim 1 , wherein said absence of said Lkb1 or decrease of the activity of said Lkb1 indicates said cancer is aggressive. 
     
     
         5 . The method of  claim 1 , wherein said presence of said intact Lkb1 indicates said cancer is not aggressive. 
     
     
         6 . The method of  claim 1 , wherein said absence of said Lkb1 or decrease of the activity of said Lkb1 indicates said cancer is metastatic. 
     
     
         7 . The method of  claim 1 , further comprising determining the presence or absence of a mutation in K-ras, EGFR or BRAF. 
     
     
         8 . A method of assessing the efficacy of a m-TOR inhibitor for treating or inhibiting the growth of lung cancer in a patient, comprising detecting inactivation of Lkb1 gene expression in a lung cancer tumor from a subject, wherein said inactivation of Lkb1 gene expression in the lung cancer tumor indicates treatment with an m-TOR inhibitor is efficacious. 
     
     
         9 . A method of diagnosing lung cancer or a predisposition to developing lung cancer in a subject, comprising determining a level of expression of an lung cancer-associated gene in a patient derived tissue sample, wherein an increase of said level compared to a normal control level of said gene indicates that said subject suffers from or is at risk of developing lung cancer. 
     
     
         10 . The method of  claim 9 , wherein said lung cancer-associated gene is selected from the group consisting of LC 1-461, wherein an increase in said level compared to a normal control level indicates said subject suffers from or is at risk of developing lung cancer. 
     
     
         11 . The method of  claim 9 , wherein said increase is at least 10% greater than said normal control level. 
     
     
         12 . The method of  claim 9 , wherein said method further comprises determining said level of expression of a plurality of lung cancer-associated genes. 
     
     
         13 . A lung cancer reference expression profile, comprising a pattern of gene expression of two or more genes selected from the group consisting of LC 1-461. 
     
     
         14 . A kit comprising a detection reagent which binds to two or more nucleic acid sequences selected from the group consisting of LC 1-461. 
     
     
         15 . An array comprising a nucleic acid which binds to two or more nucleic acid sequences selected from the group consisting of LC 1-461. 
     
     
         16 . A transgenic animal whose genome comprises a mutant K-ras oncogene and at least one Lkb1 null allele, wherein said transgenic animal constitutively expresses a mutated K-ras protein in at least one tissue and exhibits accelerated development of a lung tumor. 
     
     
         17 . The transgenic animal of  claim 16  in which said animal is homozygous null for Lkb1. 
     
     
         18 . The transgenic animal of  claim 16 , wherein said K-ras oncogen contains a G12D mutation.