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Blood, Vol. 93 No. 7 (April 1), 1999:
pp. 2158-2166
RAPID COMMUNICATION
Role of Amplified Genes in the Production of Autoantibodies
Nicole Brass,
Alexander Rácz,
Christine Bauer,
Dirk Heckel,
Gerhard Sybrecht, and
Eckart Meese
From the Department of Human Genetics and the Department of Internal
Medicine V, Medical School, University of Saarland, Homburg/Saar,
Germany.
A variety of previously published studies have shown the presence of
autoantibodies directed against oncogenic proteins in the sera of
patients with tumors. Generally the underlying genetic aberration
responsible for the induction of an immune response directed against an
abnormal protein is unknown. In our studies we analyzed the role of
gene amplification in the production of autoantibodies in squamous cell
lung carcinoma. We screened a cDNA expression library with autologous
patient serum and characterized the isolated cDNA clones encoding tumor
expressed antigens termed LCEA (lung carcinoma expressed antigens). As
determined by sequence analysis, the 35 identified cDNA clones
represent 19 different genes of both known and unknown function. The
spectrum of different clones were mapped by polymerase chain reaction
(PCR) and fluorescence in-situ hybridization, showing that a majority
are located on chromosome 3, which is frequently affected by
chromosomal abnormalities in lung cancer. Gene amplification of 14 genes was analyzed by comparative PCR. Nine genes (65% of all analyzed
genes) were found to be amplified; furthermore, most of them are also
overrepresented in the pool of cDNA clones, suggesting an
overexpression in the corresponding tumor. These results strongly
suggest that gene amplification is one possible mechanism for the
expression of immunoreactive antigens in squamous cell lung carcinoma.
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