Role of amplified genes in the production of autoantibodies

A variety of previously published studies have shown the presence of autoan tibodies directed against oncogenic proteins in the sera of patients with t umors. Generally the underlying genetic aberration responsible for the indu ction of an immune response directed against an abnormal protein is unknown . In our studies we analyzed the role of gene amplification in the producti on of autoantibodies in squamous cell lung carcinoma. We screened a cDNA ex pression library with autologous patient serum and characterized the isolat ed cDNA clones encoding tumor expressed antigens termed LCEA (lung carcinom a expressed antigens). As determined by sequence analysis, the 35 identifie d cDNA clones represent 19 different genes of both known and unknown functi on. The spectrum of different clones were mapped by polymerase chain reacti on (PCR) and fluorescence in-situ hybridization, showing that a majority ar e located on chromosome 3, which is frequently affected by chromosomal abno rmalities in lung cancer. Gene amplification of 14 genes was analyzed by co mparative PCR. Nine genes (65% of all analyzed genes) were found to be ampl ified; furthermore, most of them are also overrepresented in the pool of cD NA clones, suggesting an overexpression in the corresponding tumor. These r esults strongly suggest that gene amplification is one possible mechanism f or the expression of immunoreactive antigens in squamous cell lung carcinom a. (C) 1999 by The American Society of Hematology.