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Polymorphic variants of IGF2BP3 and SENCR have an impact on predisposition and/or progression of Ewing sarcoma

Ewing sarcoma (EWS), the second most common malignant bone tumor in children and adolescents, occurs abruptly without clear evidence of tumor history or progression. Previous association studies have identified some inherited variants associated with the risk of developing EWS but a common picture o...

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Autores principales: Martinelli, Marcella, Mancarella, Caterina, Scapoli, Luca, Palmieri, Annalisa, De Sanctis, Paola, Ferrari, Cristina, Pasello, Michela, Zucchini, Cinzia, Scotlandi, Katia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9634078/
https://www.ncbi.nlm.nih.gov/pubmed/36338681
http://dx.doi.org/10.3389/fonc.2022.968884
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author Martinelli, Marcella
Mancarella, Caterina
Scapoli, Luca
Palmieri, Annalisa
De Sanctis, Paola
Ferrari, Cristina
Pasello, Michela
Zucchini, Cinzia
Scotlandi, Katia
author_facet Martinelli, Marcella
Mancarella, Caterina
Scapoli, Luca
Palmieri, Annalisa
De Sanctis, Paola
Ferrari, Cristina
Pasello, Michela
Zucchini, Cinzia
Scotlandi, Katia
author_sort Martinelli, Marcella
collection PubMed
description Ewing sarcoma (EWS), the second most common malignant bone tumor in children and adolescents, occurs abruptly without clear evidence of tumor history or progression. Previous association studies have identified some inherited variants associated with the risk of developing EWS but a common picture of the germline susceptibility to this tumor remains largely unclear. Here, we examine the association between thirty single nucleotide polymorphisms (SNPs) of the IGF2BP3, a gene that codes for an oncofetal RNA-binding protein demonstrated to be important for EWS patient’s risk stratification, and five SNPs of SENCR, a long non-coding RNA shown to regulate IGF2BP3. An association between polymorphisms and EWS susceptibility was observed for three IGF2BP3 SNPs - rs112316332, rs13242065, rs12700421 - and for four SENCR SNPs - rs10893909, rs11221437, rs12420823, rs4526784 -. In addition, IGF2BP3 rs34033684 and SENCR rs10893909 variants increased the risk for female respect to male subgroup when carried together, while IGF2BP3 rs13242065 or rs76983703 variants reduced the probability of a disease later onset (> 14 years). Moreover, the absence of IGF2BP3 rs10488282 variant and the presence of rs199653 or rs35875486 variant were significantly associated with a worse survival in EWS patients with localized disease at diagnosis. Overall, our data provide the first evidence linking genetic variants of IGF2BP3 and its modulator SENCR to the risk of EWS development and to disease progression, thus supporting the concept that heritable factors can influence susceptibility to EWS and may help to predict patient prognosis.
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spelling pubmed-96340782022-11-05 Polymorphic variants of IGF2BP3 and SENCR have an impact on predisposition and/or progression of Ewing sarcoma Martinelli, Marcella Mancarella, Caterina Scapoli, Luca Palmieri, Annalisa De Sanctis, Paola Ferrari, Cristina Pasello, Michela Zucchini, Cinzia Scotlandi, Katia Front Oncol Oncology Ewing sarcoma (EWS), the second most common malignant bone tumor in children and adolescents, occurs abruptly without clear evidence of tumor history or progression. Previous association studies have identified some inherited variants associated with the risk of developing EWS but a common picture of the germline susceptibility to this tumor remains largely unclear. Here, we examine the association between thirty single nucleotide polymorphisms (SNPs) of the IGF2BP3, a gene that codes for an oncofetal RNA-binding protein demonstrated to be important for EWS patient’s risk stratification, and five SNPs of SENCR, a long non-coding RNA shown to regulate IGF2BP3. An association between polymorphisms and EWS susceptibility was observed for three IGF2BP3 SNPs - rs112316332, rs13242065, rs12700421 - and for four SENCR SNPs - rs10893909, rs11221437, rs12420823, rs4526784 -. In addition, IGF2BP3 rs34033684 and SENCR rs10893909 variants increased the risk for female respect to male subgroup when carried together, while IGF2BP3 rs13242065 or rs76983703 variants reduced the probability of a disease later onset (> 14 years). Moreover, the absence of IGF2BP3 rs10488282 variant and the presence of rs199653 or rs35875486 variant were significantly associated with a worse survival in EWS patients with localized disease at diagnosis. Overall, our data provide the first evidence linking genetic variants of IGF2BP3 and its modulator SENCR to the risk of EWS development and to disease progression, thus supporting the concept that heritable factors can influence susceptibility to EWS and may help to predict patient prognosis. Frontiers Media S.A. 2022-10-21 /pmc/articles/PMC9634078/ /pubmed/36338681 http://dx.doi.org/10.3389/fonc.2022.968884 Text en Copyright © 2022 Martinelli, Mancarella, Scapoli, Palmieri, De Sanctis, Ferrari, Pasello, Zucchini and Scotlandi https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Martinelli, Marcella
Mancarella, Caterina
Scapoli, Luca
Palmieri, Annalisa
De Sanctis, Paola
Ferrari, Cristina
Pasello, Michela
Zucchini, Cinzia
Scotlandi, Katia
Polymorphic variants of IGF2BP3 and SENCR have an impact on predisposition and/or progression of Ewing sarcoma
title Polymorphic variants of IGF2BP3 and SENCR have an impact on predisposition and/or progression of Ewing sarcoma
title_full Polymorphic variants of IGF2BP3 and SENCR have an impact on predisposition and/or progression of Ewing sarcoma
title_fullStr Polymorphic variants of IGF2BP3 and SENCR have an impact on predisposition and/or progression of Ewing sarcoma
title_full_unstemmed Polymorphic variants of IGF2BP3 and SENCR have an impact on predisposition and/or progression of Ewing sarcoma
title_short Polymorphic variants of IGF2BP3 and SENCR have an impact on predisposition and/or progression of Ewing sarcoma
title_sort polymorphic variants of igf2bp3 and sencr have an impact on predisposition and/or progression of ewing sarcoma
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9634078/
https://www.ncbi.nlm.nih.gov/pubmed/36338681
http://dx.doi.org/10.3389/fonc.2022.968884
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