Cargando…
Inherited germline TP53 mutation encodes a protein with an aberrant C-terminal motif in a case of pediatric adrenocortical tumor
Childhood adrenocortical tumor (ACT), a very rare malignancy, has an annual worldwide incidence of about 0.3 per million children younger than 15 years. The association between inherited germline mutations of the TP53 gene and an increased predisposition to ACT was described in the context of the Li...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
Springer Netherlands
2010
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3036813/ https://www.ncbi.nlm.nih.gov/pubmed/20967502 http://dx.doi.org/10.1007/s10689-010-9392-z |
_version_ | 1782197902268956672 |
---|---|
author | Pinto, Emilia M. Ribeiro, Raul C. Kletter, Gad B. Lawrence, John P. Jenkins, Jesse J. Wang, Jinling Shurtleff, Sheila McGregor, Lisa Kriwacki, Richard W. Zambetti, Gerard P. |
author_facet | Pinto, Emilia M. Ribeiro, Raul C. Kletter, Gad B. Lawrence, John P. Jenkins, Jesse J. Wang, Jinling Shurtleff, Sheila McGregor, Lisa Kriwacki, Richard W. Zambetti, Gerard P. |
author_sort | Pinto, Emilia M. |
collection | PubMed |
description | Childhood adrenocortical tumor (ACT), a very rare malignancy, has an annual worldwide incidence of about 0.3 per million children younger than 15 years. The association between inherited germline mutations of the TP53 gene and an increased predisposition to ACT was described in the context of the Li-Fraumeni syndrome. In fact, about two-thirds of children with ACT have a TP53 mutation. However, less than 10% of pediatric ACT cases occur in Li-Fraumeni syndrome, suggesting that inherited low-penetrance TP53 mutations play an important role in pediatric adrenal cortex tumorigenesis. We identified a novel inherited germline TP53 mutation affecting the acceptor splice site at intron 10 in a child with an ACT and no family history of cancer. The lack of family history of cancer and previous information about the carcinogenic potential of the mutation led us to further characterize it. Bioinformatics analysis showed that the non-natural and highly hydrophobic C-terminal segment of the frame-shifted mutant p53 protein may disrupt its tumor suppressor function by causing misfolding and aggregation. Our findings highlight the clinical and genetic counseling dilemmas that arise when an inherited TP53 mutation is found in a child with ACT without relatives with Li-Fraumeni-component tumors. |
format | Text |
id | pubmed-3036813 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Springer Netherlands |
record_format | MEDLINE/PubMed |
spelling | pubmed-30368132011-03-16 Inherited germline TP53 mutation encodes a protein with an aberrant C-terminal motif in a case of pediatric adrenocortical tumor Pinto, Emilia M. Ribeiro, Raul C. Kletter, Gad B. Lawrence, John P. Jenkins, Jesse J. Wang, Jinling Shurtleff, Sheila McGregor, Lisa Kriwacki, Richard W. Zambetti, Gerard P. Fam Cancer Article Childhood adrenocortical tumor (ACT), a very rare malignancy, has an annual worldwide incidence of about 0.3 per million children younger than 15 years. The association between inherited germline mutations of the TP53 gene and an increased predisposition to ACT was described in the context of the Li-Fraumeni syndrome. In fact, about two-thirds of children with ACT have a TP53 mutation. However, less than 10% of pediatric ACT cases occur in Li-Fraumeni syndrome, suggesting that inherited low-penetrance TP53 mutations play an important role in pediatric adrenal cortex tumorigenesis. We identified a novel inherited germline TP53 mutation affecting the acceptor splice site at intron 10 in a child with an ACT and no family history of cancer. The lack of family history of cancer and previous information about the carcinogenic potential of the mutation led us to further characterize it. Bioinformatics analysis showed that the non-natural and highly hydrophobic C-terminal segment of the frame-shifted mutant p53 protein may disrupt its tumor suppressor function by causing misfolding and aggregation. Our findings highlight the clinical and genetic counseling dilemmas that arise when an inherited TP53 mutation is found in a child with ACT without relatives with Li-Fraumeni-component tumors. Springer Netherlands 2010-10-22 2011 /pmc/articles/PMC3036813/ /pubmed/20967502 http://dx.doi.org/10.1007/s10689-010-9392-z Text en © The Author(s) 2010 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. |
spellingShingle | Article Pinto, Emilia M. Ribeiro, Raul C. Kletter, Gad B. Lawrence, John P. Jenkins, Jesse J. Wang, Jinling Shurtleff, Sheila McGregor, Lisa Kriwacki, Richard W. Zambetti, Gerard P. Inherited germline TP53 mutation encodes a protein with an aberrant C-terminal motif in a case of pediatric adrenocortical tumor |
title | Inherited germline TP53 mutation encodes a protein with an aberrant C-terminal motif in a case of pediatric adrenocortical tumor |
title_full | Inherited germline TP53 mutation encodes a protein with an aberrant C-terminal motif in a case of pediatric adrenocortical tumor |
title_fullStr | Inherited germline TP53 mutation encodes a protein with an aberrant C-terminal motif in a case of pediatric adrenocortical tumor |
title_full_unstemmed | Inherited germline TP53 mutation encodes a protein with an aberrant C-terminal motif in a case of pediatric adrenocortical tumor |
title_short | Inherited germline TP53 mutation encodes a protein with an aberrant C-terminal motif in a case of pediatric adrenocortical tumor |
title_sort | inherited germline tp53 mutation encodes a protein with an aberrant c-terminal motif in a case of pediatric adrenocortical tumor |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3036813/ https://www.ncbi.nlm.nih.gov/pubmed/20967502 http://dx.doi.org/10.1007/s10689-010-9392-z |
work_keys_str_mv | AT pintoemiliam inheritedgermlinetp53mutationencodesaproteinwithanaberrantcterminalmotifinacaseofpediatricadrenocorticaltumor AT ribeiroraulc inheritedgermlinetp53mutationencodesaproteinwithanaberrantcterminalmotifinacaseofpediatricadrenocorticaltumor AT klettergadb inheritedgermlinetp53mutationencodesaproteinwithanaberrantcterminalmotifinacaseofpediatricadrenocorticaltumor AT lawrencejohnp inheritedgermlinetp53mutationencodesaproteinwithanaberrantcterminalmotifinacaseofpediatricadrenocorticaltumor AT jenkinsjessej inheritedgermlinetp53mutationencodesaproteinwithanaberrantcterminalmotifinacaseofpediatricadrenocorticaltumor AT wangjinling inheritedgermlinetp53mutationencodesaproteinwithanaberrantcterminalmotifinacaseofpediatricadrenocorticaltumor AT shurtleffsheila inheritedgermlinetp53mutationencodesaproteinwithanaberrantcterminalmotifinacaseofpediatricadrenocorticaltumor AT mcgregorlisa inheritedgermlinetp53mutationencodesaproteinwithanaberrantcterminalmotifinacaseofpediatricadrenocorticaltumor AT kriwackirichardw inheritedgermlinetp53mutationencodesaproteinwithanaberrantcterminalmotifinacaseofpediatricadrenocorticaltumor AT zambettigerardp inheritedgermlinetp53mutationencodesaproteinwithanaberrantcterminalmotifinacaseofpediatricadrenocorticaltumor |