Familial cancer associated with a polymorphism in ARLTS1. Export

@article{citeulike:2588926, abstract = {BACKGROUND: The finding of hemizygous or homozygous deletions at band 14 on chromosome 13 in a variety of neoplasms suggests the presence of a tumor-suppressor locus telomeric to the RB1 gene. METHODS: We studied samples from 216 patients with various types of sporadic tumors or idiopathic pancytopenia, peripheral-blood samples from 109 patients with familial cancer or multiple cancers, and control blood samples from 475 healthy people or patients with diseases other than cancer. We performed functional studies of cell lines lacking ARLTS1 expression with the use of both the full-length ARLTS1 gene and a truncated variant. RESULTS: We found a gene at 13q14, ARLTS1, a member of the ADP-ribosylation factor family, with properties of a tumor-suppressor gene. We analyzed 800 DNA samples from tumors and blood cells from patients with sporadic or familial cancer and controls and found that the frequency of a nonsense polymorphism, G446A (Trp149Stop), was similar in controls and patients with sporadic tumors but was significantly more common among patients with familial cancer than among those in the other two groups (P=0.02; odds ratio, 5.7; 95 percent confidence interval, 1.3 to 24.8). ARLTS1 was down-regulated by promoter methylation in 25 percent of the primary tumors we analyzed. Transfection of wild-type ARLTS1 into A549 lung-cancer cells suppressed tumor formation in immunodeficient mice and induced apoptosis, whereas transfection of truncated ARLTS1 had a limited effect on apoptosis and tumor suppression. Microarray analysis revealed that the wild-type and Trp149Stop-transfected clones had different expression profiles. CONCLUSIONS: A genetic variant of ARLTS1 predisposes patients to familial cancer.}, address = {Thomas Jefferson University, Philadelphia, USA.}, author = {Calin, G. A. and Trapasso, F. and Shimizu, M. and Dumitru, C. D. and Yendamuri, S. and Godwin, A. K. and Ferracin, M. and Bernardi, G. and Chatterjee, D. and Baldassarre, G. and Rattan, S. and Alder, H. and Mabuchi, H. and Shiraishi, T. and Hansen, L. L. and Overgaard, J. and Herlea, V. and Mauro, F. R. and Dighiero, G. and Movsas, B. and Rassenti, L. and Kipps, T. and Baffa, R. and Fusco, A. and Mori, M. and Russo, G. and Liu, C. G. and Neuberg, D. and Bullrich, F. and Negrini, M. and Croce, C. M.}, citeulike-article-id = {2588926}, citeulike-linkout-0 = {http://dx.doi.org/10.1056/NEJMoa042280}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/15843669}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=15843669}, day = {21}, doi = {10.1056/NEJMoa042280}, issn = {1533-4406}, journal = {N Engl J Med}, keywords = {arlts1, arraycgh, breast-cancer, familial, loss}, month = {April}, number = {16}, pages = {1667--1676}, posted-at = {2008-03-26 10:15:37}, priority = {2}, title = {Familial cancer associated with a polymorphism in ARLTS1.}, url = {http://dx.doi.org/10.1056/NEJMoa042280}, volume = {352}, year = {2005} }

TY - JOUR ID - citeulike:2588926 L3 - citeulike-article-id:2588926 N2 - BACKGROUND: The finding of hemizygous or homozygous deletions at band 14 on chromosome 13 in a variety of neoplasms suggests the presence of a tumor-suppressor locus telomeric to the RB1 gene. METHODS: We studied samples from 216 patients with various types of sporadic tumors or idiopathic pancytopenia, peripheral-blood samples from 109 patients with familial cancer or multiple cancers, and control blood samples from 475 healthy people or patients with diseases other than cancer. We performed functional studies of cell lines lacking ARLTS1 expression with the use of both the full-length ARLTS1 gene and a truncated variant. RESULTS: We found a gene at 13q14, ARLTS1, a member of the ADP-ribosylation factor family, with properties of a tumor-suppressor gene. We analyzed 800 DNA samples from tumors and blood cells from patients with sporadic or familial cancer and controls and found that the frequency of a nonsense polymorphism, G446A (Trp149Stop), was similar in controls and patients with sporadic tumors but was significantly more common among patients with familial cancer than among those in the other two groups (P=0.02; odds ratio, 5.7; 95 percent confidence interval, 1.3 to 24.8). ARLTS1 was down-regulated by promoter methylation in 25 percent of the primary tumors we analyzed. Transfection of wild-type ARLTS1 into A549 lung-cancer cells suppressed tumor formation in immunodeficient mice and induced apoptosis, whereas transfection of truncated ARLTS1 had a limited effect on apoptosis and tumor suppression. Microarray analysis revealed that the wild-type and Trp149Stop-transfected clones had different expression profiles. CONCLUSIONS: A genetic variant of ARLTS1 predisposes patients to familial cancer. IS - 16 JF - N Engl J Med SN - 1533-4406 AD - Thomas Jefferson University, Philadelphia, USA. EP - 1676 TI - Familial cancer associated with a polymorphism in ARLTS1. VL - 352 SP - 1667 KW - arlts1 KW - arraycgh KW - breast-cancer KW - familial KW - loss AU - Calin, GA AU - Trapasso, F AU - Shimizu, M AU - Dumitru, CD AU - Yendamuri, S AU - Godwin, AK AU - Ferracin, M AU - Bernardi, G AU - Chatterjee, D AU - Baldassarre, G AU - Rattan, S AU - Alder, H AU - Mabuchi, H AU - Shiraishi, T AU - Hansen, LL AU - Overgaard, J AU - Herlea, V AU - Mauro, FR AU - Dighiero, G AU - Movsas, B AU - Rassenti, L AU - Kipps, T AU - Baffa, R AU - Fusco, A AU - Mori, M AU - Russo, G AU - Liu, CG AU - Neuberg, D AU - Bullrich, F AU - Negrini, M AU - Croce, CM PY - 2005/04/21/ UR - http://dx.doi.org/10.1056/NEJMoa042280 ER -