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Low penetrance susceptibility to glioma is caused by the TP53 variant rs78378222

BACKGROUND: Most of the heritable risk of glioma is presently unaccounted for by mutations in known genes. In addition to rare inactivating germline mutations in TP53 causing glioma in the context of the Li-Fraumeni syndrome, polymorphic variation in TP53 may also contribute to the risk of developin...

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Autores principales: Enciso-Mora, V, Hosking, F J, Di Stefano, A L, Zelenika, D, Shete, S, Broderick, P, Idbaih, A, Delattre, J-Y, Hoang-Xuan, K, Marie, Y, Labussière, M, Alentorn, A, Ciccarino, P, Rossetto, M, Armstrong, G, Liu, Y, Gousias, K, Schramm, J, Lau, C, Hepworth, S J, Schoemaker, M, Strauch, K, Müller-Nurasyid, M, Schreiber, S, Franke, A, Moebus, S, Eisele, L, Swerdlow, A, Simon, M, Bondy, M, Lathrop, M, Sanson, M, Houlston, R S
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3670481/
https://www.ncbi.nlm.nih.gov/pubmed/23571737
http://dx.doi.org/10.1038/bjc.2013.155
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author Enciso-Mora, V
Hosking, F J
Di Stefano, A L
Zelenika, D
Shete, S
Broderick, P
Idbaih, A
Delattre, J-Y
Hoang-Xuan, K
Marie, Y
Labussière, M
Alentorn, A
Ciccarino, P
Rossetto, M
Armstrong, G
Liu, Y
Gousias, K
Schramm, J
Lau, C
Hepworth, S J
Schoemaker, M
Strauch, K
Müller-Nurasyid, M
Schreiber, S
Franke, A
Moebus, S
Eisele, L
Swerdlow, A
Simon, M
Bondy, M
Lathrop, M
Sanson, M
Houlston, R S
author_facet Enciso-Mora, V
Hosking, F J
Di Stefano, A L
Zelenika, D
Shete, S
Broderick, P
Idbaih, A
Delattre, J-Y
Hoang-Xuan, K
Marie, Y
Labussière, M
Alentorn, A
Ciccarino, P
Rossetto, M
Armstrong, G
Liu, Y
Gousias, K
Schramm, J
Lau, C
Hepworth, S J
Schoemaker, M
Strauch, K
Müller-Nurasyid, M
Schreiber, S
Franke, A
Moebus, S
Eisele, L
Swerdlow, A
Simon, M
Bondy, M
Lathrop, M
Sanson, M
Houlston, R S
author_sort Enciso-Mora, V
collection PubMed
description BACKGROUND: Most of the heritable risk of glioma is presently unaccounted for by mutations in known genes. In addition to rare inactivating germline mutations in TP53 causing glioma in the context of the Li-Fraumeni syndrome, polymorphic variation in TP53 may also contribute to the risk of developing glioma. METHODS: To comprehensively evaluate the impact of variation in TP53 on risk, we analysed 23 tagSNPs and imputed 2377 unobserved genotypes in four series totaling 4147 glioma cases and 7435 controls. RESULTS: The strongest validated association signal was shown by the imputed single-nucleotide polymorphism (SNP) rs78378222 (P=6.86 × 10(−24), minor allele frequency ∼0.013). Confirmatory genotyping confirmed the high quality of the imputation. The association between rs78378222 and risk was seen for both glioblastoma multiforme (GBM) and non-GBM tumours. We comprehensively examined the relationship between rs78378222 and overall survival in two of the case series totaling 1699 individuals. Despite employing statistical tests sensitive to the detection of differences in early survival, no association was shown. CONCLUSION: Our data provided strong validation of rs78378222 as a risk factor for glioma but do not support the tenet that the polymorphism being a clinically useful prognostic marker. Acquired TP53 inactivation is a common feature of glioma. As rs78378222 changes the polyadenylation signal of TP53 leading to impaired 3′-end processing of TP53 mRNA, the SNP has strong plausibility for being directly functional contributing to the aetiological basis of glioma.
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spelling pubmed-36704812014-05-28 Low penetrance susceptibility to glioma is caused by the TP53 variant rs78378222 Enciso-Mora, V Hosking, F J Di Stefano, A L Zelenika, D Shete, S Broderick, P Idbaih, A Delattre, J-Y Hoang-Xuan, K Marie, Y Labussière, M Alentorn, A Ciccarino, P Rossetto, M Armstrong, G Liu, Y Gousias, K Schramm, J Lau, C Hepworth, S J Schoemaker, M Strauch, K Müller-Nurasyid, M Schreiber, S Franke, A Moebus, S Eisele, L Swerdlow, A Simon, M Bondy, M Lathrop, M Sanson, M Houlston, R S Br J Cancer Genetics and Genomics BACKGROUND: Most of the heritable risk of glioma is presently unaccounted for by mutations in known genes. In addition to rare inactivating germline mutations in TP53 causing glioma in the context of the Li-Fraumeni syndrome, polymorphic variation in TP53 may also contribute to the risk of developing glioma. METHODS: To comprehensively evaluate the impact of variation in TP53 on risk, we analysed 23 tagSNPs and imputed 2377 unobserved genotypes in four series totaling 4147 glioma cases and 7435 controls. RESULTS: The strongest validated association signal was shown by the imputed single-nucleotide polymorphism (SNP) rs78378222 (P=6.86 × 10(−24), minor allele frequency ∼0.013). Confirmatory genotyping confirmed the high quality of the imputation. The association between rs78378222 and risk was seen for both glioblastoma multiforme (GBM) and non-GBM tumours. We comprehensively examined the relationship between rs78378222 and overall survival in two of the case series totaling 1699 individuals. Despite employing statistical tests sensitive to the detection of differences in early survival, no association was shown. CONCLUSION: Our data provided strong validation of rs78378222 as a risk factor for glioma but do not support the tenet that the polymorphism being a clinically useful prognostic marker. Acquired TP53 inactivation is a common feature of glioma. As rs78378222 changes the polyadenylation signal of TP53 leading to impaired 3′-end processing of TP53 mRNA, the SNP has strong plausibility for being directly functional contributing to the aetiological basis of glioma. Nature Publishing Group 2013-05-28 2013-04-09 /pmc/articles/PMC3670481/ /pubmed/23571737 http://dx.doi.org/10.1038/bjc.2013.155 Text en Copyright © 2013 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/3.0/ From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
spellingShingle Genetics and Genomics
Enciso-Mora, V
Hosking, F J
Di Stefano, A L
Zelenika, D
Shete, S
Broderick, P
Idbaih, A
Delattre, J-Y
Hoang-Xuan, K
Marie, Y
Labussière, M
Alentorn, A
Ciccarino, P
Rossetto, M
Armstrong, G
Liu, Y
Gousias, K
Schramm, J
Lau, C
Hepworth, S J
Schoemaker, M
Strauch, K
Müller-Nurasyid, M
Schreiber, S
Franke, A
Moebus, S
Eisele, L
Swerdlow, A
Simon, M
Bondy, M
Lathrop, M
Sanson, M
Houlston, R S
Low penetrance susceptibility to glioma is caused by the TP53 variant rs78378222
title Low penetrance susceptibility to glioma is caused by the TP53 variant rs78378222
title_full Low penetrance susceptibility to glioma is caused by the TP53 variant rs78378222
title_fullStr Low penetrance susceptibility to glioma is caused by the TP53 variant rs78378222
title_full_unstemmed Low penetrance susceptibility to glioma is caused by the TP53 variant rs78378222
title_short Low penetrance susceptibility to glioma is caused by the TP53 variant rs78378222
title_sort low penetrance susceptibility to glioma is caused by the tp53 variant rs78378222
topic Genetics and Genomics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3670481/
https://www.ncbi.nlm.nih.gov/pubmed/23571737
http://dx.doi.org/10.1038/bjc.2013.155
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