dc.creator | YAO, Li | |
dc.creator | SCHIAVI, Francesca | |
dc.creator | CASCON, Alberto | |
dc.creator | QIN, Yuejuan | |
dc.creator | INGLADA-PEREZ, Lucia | |
dc.creator | KING, Elizabeth E. | |
dc.creator | TOLEDO, Rodrigo A. | |
dc.creator | ERCOLINO, Tonino | |
dc.creator | RAPIZZI, Elena | |
dc.creator | RICKETTS, Christopher J. | |
dc.creator | MORI, Luigi | |
dc.creator | GIACCHE, Mara | |
dc.creator | MENDOLA, Antonella | |
dc.creator | TASCHIN, Elisa | |
dc.creator | BOARETTO, Francesca | |
dc.creator | LOLI, Paola | |
dc.creator | IACOBONE, Maurizio | |
dc.creator | ROSSI, Gian-Paolo | |
dc.creator | BIONDI, Bernadette | |
dc.creator | LIMA-JUNIOR, Jose Viana | |
dc.creator | KATER, Claudio E. | |
dc.creator | BEX, Marie | |
dc.creator | VIKKULA, Miikka | |
dc.creator | GROSSMAN, Ashley B. | |
dc.creator | GRUBER, Stephen B. | |
dc.creator | BARONTINI, Marta | |
dc.creator | PERSU, Alexandre | |
dc.creator | CASTELLANO, Maurizio | |
dc.creator | TOLEDO, Sergio P. A. | |
dc.creator | MAHER, Eamonn R. | |
dc.creator | MANNELLI, Massimo | |
dc.creator | OPOCHER, Giuseppe | |
dc.creator | ROBLEDO, Mercedes | |
dc.creator | DAHIA, Patricia L. M. | |
dc.date.accessioned | 2012-10-19T17:08:56Z | |
dc.date.accessioned | 2018-07-04T15:05:34Z | |
dc.date.available | 2012-10-19T17:08:56Z | |
dc.date.available | 2018-07-04T15:05:34Z | |
dc.date.created | 2012-10-19T17:08:56Z | |
dc.date.issued | 2010 | |
dc.identifier | JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, v.304, n.23, p.2611-2619, 2010 | |
dc.identifier | 0098-7484 | |
dc.identifier | http://producao.usp.br/handle/BDPI/21696 | |
dc.identifier | 10.1001/jama.2010.1830 | |
dc.identifier | http://dx.doi.org/10.1001/jama.2010.1830 | |
dc.identifier.uri | http://repositorioslatinoamericanos.uchile.cl/handle/2250/1618470 | |
dc.description.abstract | Context Pheochromocytomas and paragangliomas are genetically heterogeneous neural crest-derived neoplasms. We recently identified germline mutations of the novel transmembrane-encoding gene FP/TMEM127 in familial and sporadic pheochromocytomas consistent with a tumor suppressor effect. Objectives To examine the prevalence and spectrum of FP/TMEM127 mutations in pheochromocytomas and paragangliomas and to test the effect of mutations in vitro. Design, Setting, and Participants We sequenced the FP/TMEM127 gene in 990 individuals with pheochromocytomas and/or paragangliomas, including 898 previously unreported cases without mutations in other susceptibility genes from 8 independent worldwide referral centers between January 2009 and June 2010. A multiplex polymerase chain reaction-based method was developed to screen for large gene deletions in 545 of these samples. Confocal microscopy of 5 transfected mutant proteins was used to determine their subcellular localization. Main Outcome Measures The frequency and type of FP/TMEM127 mutation or deletion was assessed and correlated with clinical variables; the subcellular localization of 5 overexpressed mutants was compared with wild-type FP/TMEM127 protein. Results We identified 19 potentially pathogenic FP/TMEM127 germline mutations in 20 independent families, but no large deletions were detected. All mutation carriers had adrenal tumors, including 7 bilateral (P=2.7 x 10(-4)) and/or with familial disease (5 of 20 samples; P=.005). The median age at disease onset in the FP/TMEM127 mutation group was similar to that of patients without a mutation (41.5 vs 45 years, respectively; P=.54). The most common presentation was that of a single benign adrenal tumor in patients older than 40 years. Malignancy was seen in 1 mutation carrier (5%). Expression of 5 novel FP/TMEM127 mutations in cell lines revealed diffuse localization of the mutant proteins in contrast with the discrete multiorganelle distribution of wild-type TMEM127. Conclusions Germline mutations of FP/TMEM127 were associated with pheochromocytoma but not paraganglioma and occured in an age group frequently excluded from genetic screening algorithms. Disease-associated mutations disrupt intracellular distribution of the FP/TMEM127 protein. JAMA. 2010;304(23):2611-2619 www.jama.com | |
dc.language | eng | |
dc.publisher | AMER MEDICAL ASSOC | |
dc.relation | Jama-journal of the American Medical Association | |
dc.rights | Copyright AMER MEDICAL ASSOC | |
dc.rights | restrictedAccess | |
dc.title | Spectrum and Prevalence of FP/TMEM127 Gene Mutations in Pheochromocytomas and Paragangliomas | |
dc.type | Artículos de revistas | |