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A decade long search for antigenic proteins in cancer have uncovered a number of proteins that are common targets of the cancer patients immune system and thus, might be suitable for immunotherapy as well as early diagnosis of lung cancer.In support of the first possibility we have demonstrated a clear correlation between anti-tumor antigen responses to SOX2 antigen and better prognosis in small cell lung cancer patients, as well as patients with monoclonal gammopathy of undetermined significance (MGUS).To define a panel of antigens that could be utilized for the (early) diagnosis of lung cancer with a high sensitivity and specificity we have undertaken a systemic analysis of antigen panels representative of the human proteome.Cancer-testis (or cancer-germline, CT) antigens are the only group of genes known to be coordinately upregnlated in a large percentage of cancer that also show a tissue-specific distribution.The mechanisms underlying CT gene expression that are primarily epigenetic include chromosomal conformations that are deranged upon tumorigenic transformation.Paired analyses of potential tumor suppressor and CT genes on the X chromosome in tumors reveal epigenetic junctions and boundaries of chromosomal secondary structures which are novel indicators of transformation as well as useful biomarkers.