The paternally expressed gene PEG10 is a retrotransposon derived gene adapted through mammalian evolution located on human chromosome 7q21. PEG10 codes for at least two proteins, PEG10-RF1 and PEG10-RF1/2, by -1 frameshift translation. Overexpression or reinduced PEG10 expression was seen in malignancies, like hepatocellular carcinoma or B-cell acute and chronic lymphocytic leukemia. PEG10 was also shown to promote adipocyte differentiation. Experimental evidence suggests that the PEG10-RF1 protein is an inhibitor of apoptosis and mediates cell proliferation. Here we present new data on the genomic organization of PEG10 by identifying the major transcription start site, a new splice variant and report the cloning and analysis of 1.9 kb of the PEG10 promoter. Furthermore, we show for the first time that PEG10 translation is initiated at a non-AUG start codon upstream of the previously predicted AUG codon as well as at the AUG codon. The finding that PEG10 translation is initiated at different sides adds a new aspect to the already interesting feature of PEG10's −1 frameshift translation mechanism. It is now important to unravel the cellular functions of the PEG10 protein variants and how they are related to normal or pathological conditions. The generated promoter-reporter constructs can be used for future studies to investigate how PEG10 expression is regulated. In summary, our study provides new data on the genomic organization as well as expression and translation of PEG10, a prerequisite in order to study and understand the role of PEG10 in cancer, embryonic development and normal cell homeostasis.

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With few exceptions, autoantibodies directed against the gene product of the tumor suppressor gene p53 are only detected in cancer patients. From 73 patients with various autoimmune diseases, we obtained 17 sera with elevated autoantibodies against the p53 protein comprising patients with SLE, Graves' disease, and immune vasculitis including Wegener's granulomatosis. The overall prevalence (23%) of p53 autoantibodies was comparable to that in various cancers; differences, however, were obvious with respect to the magnitude of antibody levels. Only 5% of seropositive colorectal cancer patients had levels within the critical range (150-180 U/ml) but nearly half (41%) of seropositive autoimmune disease patients were that low. None of the autoimmune disease patients exceeded 300 U/ml serum compared to more than 60% of seropositive colorectal cancer patients with higher levels. This remarkable difference in magnitude underlines the necessity of quantification of p53 autoantibodies over a mere qualitative determination. Patients with autoimmune diseases face an increased risk for malignancies. It still remains to be established whether p53 seropositivity in autoimmune diseases adds to the rare exceptions of p53AAb in non-malignant diseases or is indicative for a yet occult cancer.

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