Molecular diagnosis and typing of lung cancer variants

Abstract

Compositions and methods useful in determining the major morphological types of lung cancer are provided. The methods include detecting expression of at least one gene or biomarker in a sample. The expression of the gene or biomarker is indicative of the lung tumor subtype. The compositions include subsets of genes that are monitored for gene expression. The gene expression is capable of distinguishing between normal lung parenchyma and the major morphological types of lung cancer. The gene expression and somatic mutation data are useful in developing a complete classification of lung cancer that is prognostic and predictive for therapeutic response. The methods are suited for analysis of paraffin-embedded tissues. Methods of the invention include means for monitoring gene or biomarker expression including PCR and antibody-based detection. The biomarkers of the invention are genes and/or proteins that are selectively expressed at a high or low level in certain tumor subtypes. Biomarker expression can be assessed at the protein or nucleic acid level.

1 . A method for diagnosing lung cancer in a patient, said method comprising detecting expression of at least one nuclear biomarker in a body sample from the patient, wherein the detection of expression of said nuclear biomarker specifically identifies samples that are indicative of a lung cancer subtype and wherein said sample is paraffin embedded. 
     
     
         2 . The method of  claim 1 , wherein detecting expression comprises using at least one antibody to detect biomarker protein expression. 
     
     
         3 . The method of  claim 2 , wherein the method comprises performing immunocytochemistry. 
     
     
         4 . The method of  claim 1 , wherein expression of the nuclear biomarker is detected at the nucleic acid level. 
     
     
         5 . The method of  claim 4 , wherein detecting expression comprises performing quantitative RT-PCR. 
     
     
         6 . The method of  claim 1 , wherein the sample comprises lung cells embedded in paraffin. 
     
     
         7 . A method for diagnosing lung cancer in a patient, said method comprising detecting expression of at least two biomarkers in a body sample from the patient, wherein the detection of expression of said biomarkers specifically identifies samples that are indicative of a lung cancer subtype. 
     
     
         8 . The method of  claim 7 , wherein said nuclear biomarker is a gene set forth in Table 1. 
     
     
         9 . A method for diagnosing lung cancer in a patient, said method comprising:
 a) obtaining a lung biopsy sample from said patient;   b) contacting said sample with at least two antibodies, wherein each of said antibodies specifically binds to a distinct biomarker protein that is selectively expressed in lung cancer subtypes; and,   c) detecting binding of said antibodies to said biomarker proteins.   
     
     
         10 . A kit comprising at least two antibodies, wherein each of said antibodies specifically binds to a distinct biomarker protein that is selectively expressed in lung cancer cells. 
     
     
         11 . A method for diagnosing lung cancer in a patient comprising detecting expression of at least one nucleic acid molecule that encodes a biomarker that is selectively expressed in lung cancer cells, wherein the nuclear biomarker is selected from the group consisting of the biomarker genes set forth in Table 1, the method comprising:
 a) obtaining a lung sample from the patient;   b) isolating nucleic acid material from the sample;   c) mixing said nucleic acid material with at least one pair of oligonucleotide primers specific for the biomarker and a thermostable DNA polymerase under conditions that are suitable for amplification by polymerase chain reaction (PCR);   d) performing PCR; and,   e) detecting PCR amplification products.   
     
     
         12 . The method of  claim 11 , wherein performing PCR comprises performing RT-PCR. 
     
     
         13 . A kit comprising at least one pair of oligonucleotide primers specific for a nuclear biomarker that is selectively expressed in lung cancer. 
     
     
         14 . A kit comprising at least two pairs of oligonucleotide primers, wherein each pair of oligonucleotide primers is specific for a biomarker that is selectively expressed in a lung cancer subtype.