PMID:24310608

Citation	Joseph, CG, Darrah, E, Shah, AA, Skora, AD, Casciola-Rosen, LA, Wigley, FM, Boin, F, Fava, A, Thoburn, C, Kinde, I, Jiao, Y, Papadopoulos, N, Kinzler, KW, Vogelstein, B and Rosen, A (2014) Association of the autoimmune disease scleroderma with an immunologic response to cancer. Science 343:152-7
Abstract	Autoimmune diseases are thought to be initiated by exposures to foreign antigens that cross-react with endogenous molecules. Scleroderma is an autoimmune connective tissue disease in which patients make antibodies to a limited group of autoantigens, including RPC1, encoded by the POLR3A gene. As patients with scleroderma and antibodies against RPC1 are at increased risk for cancer, we hypothesized that the "foreign" antigens in this autoimmune disease are encoded by somatically mutated genes in the patients' incipient cancers. Studying cancers from scleroderma patients, we found genetic alterations of the POLR3A locus in six of eight patients with antibodies to RPC1 but not in eight patients without antibodies to RPC1. Analyses of peripheral blood lymphocytes and serum suggested that POLR3A mutations triggered cellular immunity and cross-reactive humoral immune responses. These results offer insight into the pathogenesis of scleroderma and provide support for the idea that acquired immunity helps to control naturally occurring cancers.
Links	PubMed Online version:10.1126/science.1246886
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Significance

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:Q7Z755		GO:0003899: DNA-directed RNA polymerase activity	ECO:0000315:		F		Table 2 shows that the ratio of mutated patients were low and the control patients had 100& to give or take 3.1% percent ratio of the SNP's. The POLR3A protein was only found in mutated patients, control patients were not heterozygous for the gene.	complete

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