MEN1 Gene Mutation and Reduced Expression Are Associated With Poor Prognosis in Pulmonary Carcinoids
Data(s) |
01/02/2014
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Resumo |
Context: MEN1 gene alterations have been implicated in lung carcinoids, but their effect on gene expression and disease outcome is unknown. Objective: Our objective was to analyze MEN1 gene and expression anomalies in lung neuroendocrine neoplasms and their correlations with clinicopathologic data and disease outcome. Design: We examined 74 lung neuroendocrine neoplasms including 58 carcinoids and 16 high-grade neuroendocrine carcinomas (HGNECs) for MEN1 mutations (n = 70) and allelic losses (n = 69), promoter hypermethylation (n = 65), and mRNA (n = 74) expression. Results were correlated with disease outcome. Results: MEN1 mutations were found in 7 of 55 (13%) carcinoids and in 1 HGNEC, mostly associated with loss of the second allele. MEN1 decreased expression levels correlated with the presence of mutations (P = .0060) and was also lower in HGNECs than carcinoids (P = .0024). MEN1 methylation was not associated with mRNA expression levels. Patients with carcinoids harboring MEN1 mutation and loss had shorter overall survival (P = .039 and P = .035, respectively) and low MEN1 mRNA levels correlated with distant metastasis (P = .00010) and shorter survival (P = .0071). In multivariate analysis, stage and MEN1 allelic loss were independent predictors of prognosis. Conclusion: Thirteen percent of pulmonary carcinoids harbor MEN1 mutation associated with reduced mRNA expression and poor prognosis. Also in mutation-negative tumors, low MEN1 gene expression correlates with an adverse disease outcome. Hypermethylation was excluded as the underlying mechanism. |
Formato |
application/pdf |
Identificador |
http://boris.unibe.ch/45136/1/jc.pdf Swarts, Dorian R. A.; Scarpa, Aldo; Corbo, Vincenzo; Van Criekinge, Wim; van Engeland, Manon; Gatti, Gaia; Henfling, Mieke E. R.; Papotti, Mauro; Perren, Aurel; Ramaekers, Frans C. S.; Speel, Ernst-Jan M.; Volante, Marco (2014). MEN1 Gene Mutation and Reduced Expression Are Associated With Poor Prognosis in Pulmonary Carcinoids. Journal of clinical endocrinology and metabolism, 99(2), E374-E378. Endocrine Society 10.1210/jc.2013-2782 <http://dx.doi.org/10.1210/jc.2013-2782> doi:10.7892/boris.45136 info:doi:10.1210/jc.2013-2782 info:pmid:24276465 urn:issn:0021-972X |
Idioma(s) |
eng |
Publicador |
Endocrine Society |
Relação |
http://boris.unibe.ch/45136/ |
Direitos |
info:eu-repo/semantics/restrictedAccess |
Fonte |
Swarts, Dorian R. A.; Scarpa, Aldo; Corbo, Vincenzo; Van Criekinge, Wim; van Engeland, Manon; Gatti, Gaia; Henfling, Mieke E. R.; Papotti, Mauro; Perren, Aurel; Ramaekers, Frans C. S.; Speel, Ernst-Jan M.; Volante, Marco (2014). MEN1 Gene Mutation and Reduced Expression Are Associated With Poor Prognosis in Pulmonary Carcinoids. Journal of clinical endocrinology and metabolism, 99(2), E374-E378. Endocrine Society 10.1210/jc.2013-2782 <http://dx.doi.org/10.1210/jc.2013-2782> |
Palavras-Chave | #570 Life sciences; biology #610 Medicine & health |
Tipo |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion PeerReviewed |