TP53 p.R337H is a conditional cancer-predisposing mutation : further evidence from a homozygous patient
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/110028 |
Resumo: | Background: Adrenocortical carcinomas (ACCs) are among the most common childhood cancers occurring in infants affected with the Li-Fraumeni and Li- Fraumeni-like (LFS/LFL) syndromes, which are caused by dominant germline mutations in the TP53 gene. In Brazil, a particular mutation, occurring in the tetramerisation domain of the gene, p.R337H, is exceedingly common due to a founder effect and is strongly associated with ACC. In this report, we describe the phenotype and long-term clinical follow-up of a female child diagnosed with ACC and homozygous for the TP53 p.R337H founder mutation. Case presentation: At age 11 months, the patient was diagnosed with a virilising anaplastic adrenal cortical tumour, which was completely excised without disturbing the adrenal capsule. Family history was consistent with an LFL tumour pattern, and genotyping identified the TP53 p.R337H mutation in both alleles in genomic DNA from lymphocytes and fibroblasts. Haplotype analysis confirmed the occurrence of the mutation in the same founder haplotype previously described in other Brazilian patients. No other germline or somatic TP53 mutations or rearrangements were identified. At age 9 years, the child was asymptomatic and had no evidence of endocrine derangements. Full body and brain magnetic resonance imaging (MRI) failed to detect any suspicious proliferative lesions, and cardiopulmonary exercise testing results were within the normal reference for the child’s age, ruling out a major exercise capacity deficiency. Conclusion: This is the first clinical and aerobic functional capacity documentation of a patient who carries two mutant TP53 alleles and no wild-type allele. Our results support the hypothesis that TP53 p.R337H, the most common TP53 mutation ever described in any population, is a conditional mutant. Furthermore, our observations over a long period of clinical follow-up suggest that TP53 p.R337H homozygotes do not have a more severe disease phenotype than do heterozygote carriers of the same mutation. Patients with the homozygous TP53 p.R337H genotype will require careful surveillance for lifetime cancer risk and for effects on metabolic capacity later in life. |
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Giacomazzi, JulianaSelistre, Simone Geiger de AlmeidaDuarte, Juliana ÁvilaRibeiro, Jorge PintoVieira, Paulo José CardosoMacedo, Gabriel de SouzaRossi, CristinaCzepielewski, Mauro AntonioNetto, Cristina Brinckmann OliveiraHainaut, PierreProlla, Patrícia Ashton2015-02-12T02:15:03Z20131471-2407http://hdl.handle.net/10183/110028000883481Background: Adrenocortical carcinomas (ACCs) are among the most common childhood cancers occurring in infants affected with the Li-Fraumeni and Li- Fraumeni-like (LFS/LFL) syndromes, which are caused by dominant germline mutations in the TP53 gene. In Brazil, a particular mutation, occurring in the tetramerisation domain of the gene, p.R337H, is exceedingly common due to a founder effect and is strongly associated with ACC. In this report, we describe the phenotype and long-term clinical follow-up of a female child diagnosed with ACC and homozygous for the TP53 p.R337H founder mutation. Case presentation: At age 11 months, the patient was diagnosed with a virilising anaplastic adrenal cortical tumour, which was completely excised without disturbing the adrenal capsule. Family history was consistent with an LFL tumour pattern, and genotyping identified the TP53 p.R337H mutation in both alleles in genomic DNA from lymphocytes and fibroblasts. Haplotype analysis confirmed the occurrence of the mutation in the same founder haplotype previously described in other Brazilian patients. No other germline or somatic TP53 mutations or rearrangements were identified. At age 9 years, the child was asymptomatic and had no evidence of endocrine derangements. Full body and brain magnetic resonance imaging (MRI) failed to detect any suspicious proliferative lesions, and cardiopulmonary exercise testing results were within the normal reference for the child’s age, ruling out a major exercise capacity deficiency. Conclusion: This is the first clinical and aerobic functional capacity documentation of a patient who carries two mutant TP53 alleles and no wild-type allele. Our results support the hypothesis that TP53 p.R337H, the most common TP53 mutation ever described in any population, is a conditional mutant. Furthermore, our observations over a long period of clinical follow-up suggest that TP53 p.R337H homozygotes do not have a more severe disease phenotype than do heterozygote carriers of the same mutation. Patients with the homozygous TP53 p.R337H genotype will require careful surveillance for lifetime cancer risk and for effects on metabolic capacity later in life.application/pdfengBMC cancer. London. Vol. 13 (2013), 187, 8 p.Genes p53Síndrome de Li-FraumeniEstudos de casosTP53 p.R337H is a conditional cancer-predisposing mutation : further evidence from a homozygous patientEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSORIGINAL000883481.pdf000883481.pdfTexto completo (inglês)application/pdf685949http://www.lume.ufrgs.br/bitstream/10183/110028/1/000883481.pdf015f8d7c2ed4112c3d5b2eb3ed7b1210MD51TEXT000883481.pdf.txt000883481.pdf.txtExtracted Texttext/plain38977http://www.lume.ufrgs.br/bitstream/10183/110028/2/000883481.pdf.txt0a215779f0e3fe1b32cc325a63b158a8MD52THUMBNAIL000883481.pdf.jpg000883481.pdf.jpgGenerated Thumbnailimage/jpeg1903http://www.lume.ufrgs.br/bitstream/10183/110028/3/000883481.pdf.jpg4434d8590eec5d786c461c8df9225f55MD5310183/1100282021-03-09 04:38:07.455909oai:www.lume.ufrgs.br:10183/110028Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2021-03-09T07:38:07Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
TP53 p.R337H is a conditional cancer-predisposing mutation : further evidence from a homozygous patient |
title |
TP53 p.R337H is a conditional cancer-predisposing mutation : further evidence from a homozygous patient |
spellingShingle |
TP53 p.R337H is a conditional cancer-predisposing mutation : further evidence from a homozygous patient Giacomazzi, Juliana Genes p53 Síndrome de Li-Fraumeni Estudos de casos |
title_short |
TP53 p.R337H is a conditional cancer-predisposing mutation : further evidence from a homozygous patient |
title_full |
TP53 p.R337H is a conditional cancer-predisposing mutation : further evidence from a homozygous patient |
title_fullStr |
TP53 p.R337H is a conditional cancer-predisposing mutation : further evidence from a homozygous patient |
title_full_unstemmed |
TP53 p.R337H is a conditional cancer-predisposing mutation : further evidence from a homozygous patient |
title_sort |
TP53 p.R337H is a conditional cancer-predisposing mutation : further evidence from a homozygous patient |
author |
Giacomazzi, Juliana |
author_facet |
Giacomazzi, Juliana Selistre, Simone Geiger de Almeida Duarte, Juliana Ávila Ribeiro, Jorge Pinto Vieira, Paulo José Cardoso Macedo, Gabriel de Souza Rossi, Cristina Czepielewski, Mauro Antonio Netto, Cristina Brinckmann Oliveira Hainaut, Pierre Prolla, Patrícia Ashton |
author_role |
author |
author2 |
Selistre, Simone Geiger de Almeida Duarte, Juliana Ávila Ribeiro, Jorge Pinto Vieira, Paulo José Cardoso Macedo, Gabriel de Souza Rossi, Cristina Czepielewski, Mauro Antonio Netto, Cristina Brinckmann Oliveira Hainaut, Pierre Prolla, Patrícia Ashton |
author2_role |
author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Giacomazzi, Juliana Selistre, Simone Geiger de Almeida Duarte, Juliana Ávila Ribeiro, Jorge Pinto Vieira, Paulo José Cardoso Macedo, Gabriel de Souza Rossi, Cristina Czepielewski, Mauro Antonio Netto, Cristina Brinckmann Oliveira Hainaut, Pierre Prolla, Patrícia Ashton |
dc.subject.por.fl_str_mv |
Genes p53 Síndrome de Li-Fraumeni Estudos de casos |
topic |
Genes p53 Síndrome de Li-Fraumeni Estudos de casos |
description |
Background: Adrenocortical carcinomas (ACCs) are among the most common childhood cancers occurring in infants affected with the Li-Fraumeni and Li- Fraumeni-like (LFS/LFL) syndromes, which are caused by dominant germline mutations in the TP53 gene. In Brazil, a particular mutation, occurring in the tetramerisation domain of the gene, p.R337H, is exceedingly common due to a founder effect and is strongly associated with ACC. In this report, we describe the phenotype and long-term clinical follow-up of a female child diagnosed with ACC and homozygous for the TP53 p.R337H founder mutation. Case presentation: At age 11 months, the patient was diagnosed with a virilising anaplastic adrenal cortical tumour, which was completely excised without disturbing the adrenal capsule. Family history was consistent with an LFL tumour pattern, and genotyping identified the TP53 p.R337H mutation in both alleles in genomic DNA from lymphocytes and fibroblasts. Haplotype analysis confirmed the occurrence of the mutation in the same founder haplotype previously described in other Brazilian patients. No other germline or somatic TP53 mutations or rearrangements were identified. At age 9 years, the child was asymptomatic and had no evidence of endocrine derangements. Full body and brain magnetic resonance imaging (MRI) failed to detect any suspicious proliferative lesions, and cardiopulmonary exercise testing results were within the normal reference for the child’s age, ruling out a major exercise capacity deficiency. Conclusion: This is the first clinical and aerobic functional capacity documentation of a patient who carries two mutant TP53 alleles and no wild-type allele. Our results support the hypothesis that TP53 p.R337H, the most common TP53 mutation ever described in any population, is a conditional mutant. Furthermore, our observations over a long period of clinical follow-up suggest that TP53 p.R337H homozygotes do not have a more severe disease phenotype than do heterozygote carriers of the same mutation. Patients with the homozygous TP53 p.R337H genotype will require careful surveillance for lifetime cancer risk and for effects on metabolic capacity later in life. |
publishDate |
2013 |
dc.date.issued.fl_str_mv |
2013 |
dc.date.accessioned.fl_str_mv |
2015-02-12T02:15:03Z |
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Estrangeiro info:eu-repo/semantics/article |
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1471-2407 |
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000883481 |
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1471-2407 000883481 |
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http://hdl.handle.net/10183/110028 |
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BMC cancer. London. Vol. 13 (2013), 187, 8 p. |
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