Risk of Optic Pathway Glioma in Neurofibromatosis Type 1: No Evidence of Genotype–Phenotype Correlations in A Large Independent Cohort
The occurrence of optic pathway gliomas (OPGs) in children with neurofibromatosis type 1 (NF1) still raises many questions regarding screening and surveillance because of the lack of robust prognostic factors. Recent studies of an overall cohort of 381 patients have suggested that the genotype may b...
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MDPI AG
2019-11-01
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Series: | Cancers |
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Online Access: | https://www.mdpi.com/2072-6694/11/12/1838 |
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doaj-859c43c852d3461ba4a14606c5706633 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Giulia Melloni Marica Eoli Claudia Cesaretti Donatella Bianchessi Maria Cristina Ibba Silvia Esposito Giulietta Scuvera Guido Morcaldi Roberto Micheli Elena Piozzi Sabrina Avignone Luisa Chiapparini Chiara Pantaleoni Federica Natacci Gaetano Finocchiaro and Veronica Saletti |
spellingShingle |
Giulia Melloni Marica Eoli Claudia Cesaretti Donatella Bianchessi Maria Cristina Ibba Silvia Esposito Giulietta Scuvera Guido Morcaldi Roberto Micheli Elena Piozzi Sabrina Avignone Luisa Chiapparini Chiara Pantaleoni Federica Natacci Gaetano Finocchiaro and Veronica Saletti Risk of Optic Pathway Glioma in Neurofibromatosis Type 1: No Evidence of Genotype–Phenotype Correlations in A Large Independent Cohort Cancers key words: neurofibromatosis type 1 nf1 gene optic pathway glioma genotype–phenotype correlations |
author_facet |
Giulia Melloni Marica Eoli Claudia Cesaretti Donatella Bianchessi Maria Cristina Ibba Silvia Esposito Giulietta Scuvera Guido Morcaldi Roberto Micheli Elena Piozzi Sabrina Avignone Luisa Chiapparini Chiara Pantaleoni Federica Natacci Gaetano Finocchiaro and Veronica Saletti |
author_sort |
Giulia Melloni |
title |
Risk of Optic Pathway Glioma in Neurofibromatosis Type 1: No Evidence of Genotype–Phenotype Correlations in A Large Independent Cohort |
title_short |
Risk of Optic Pathway Glioma in Neurofibromatosis Type 1: No Evidence of Genotype–Phenotype Correlations in A Large Independent Cohort |
title_full |
Risk of Optic Pathway Glioma in Neurofibromatosis Type 1: No Evidence of Genotype–Phenotype Correlations in A Large Independent Cohort |
title_fullStr |
Risk of Optic Pathway Glioma in Neurofibromatosis Type 1: No Evidence of Genotype–Phenotype Correlations in A Large Independent Cohort |
title_full_unstemmed |
Risk of Optic Pathway Glioma in Neurofibromatosis Type 1: No Evidence of Genotype–Phenotype Correlations in A Large Independent Cohort |
title_sort |
risk of optic pathway glioma in neurofibromatosis type 1: no evidence of genotype–phenotype correlations in a large independent cohort |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2019-11-01 |
description |
The occurrence of optic pathway gliomas (OPGs) in children with neurofibromatosis type 1 (NF1) still raises many questions regarding screening and surveillance because of the lack of robust prognostic factors. Recent studies of an overall cohort of 381 patients have suggested that the genotype may be the main determinant of the development of OPG, with the risk being higher in patients harbouring <i>NF1 </i>mutations in the 5’ tertile and the cysteine/serine-rich domain. In an attempt to confirm this hypothesis, we used strict criteria to select a large independent cohort of 309 NF1 patients with defined constitutional NF1 mutations and appropriate brain images (255 directly enrolled and 54 as a result of a literature search). One hundred and thirty-two patients had OPG and 177 did not. The association of the position (tertiles and functional domains) and type of <i>NF1</i> mutation with the development of OPG was analysed using the χ2 test and Fisher’s exact probability test; odds ratios (ORs) with 95% confidence intervals were calculated, and Bonferroni’s correction for multiple comparisons was applied; multiple logistic regression was also used to study genotype−phenotype associations further. Our findings show no significant correlation between the site/type of NF1 mutation and the risk of OPG, and thus do not support the hypothesis that certain constitutional mutations provide prognostic information in this regard. In addition, we combined our cohort with a previously described cohort of 381 patients for a total of 690 patients and statistically re-analysed the results. The re-analysis confirmed that there were no correlations between the site (tertile and domain) and the risk of OPG, thus further strengthening our conclusions. |
topic |
key words: neurofibromatosis type 1 nf1 gene optic pathway glioma genotype–phenotype correlations |
url |
https://www.mdpi.com/2072-6694/11/12/1838 |
work_keys_str_mv |
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doaj-859c43c852d3461ba4a14606c57066332020-11-25T01:15:07ZengMDPI AGCancers2072-66942019-11-011112183810.3390/cancers11121838cancers11121838Risk of Optic Pathway Glioma in Neurofibromatosis Type 1: No Evidence of Genotype–Phenotype Correlations in A Large Independent CohortGiulia Melloni0Marica Eoli1Claudia Cesaretti2Donatella Bianchessi3Maria Cristina Ibba4Silvia Esposito5Giulietta Scuvera6Guido Morcaldi7Roberto Micheli8Elena Piozzi9Sabrina Avignone10Luisa Chiapparini11Chiara Pantaleoni12Federica Natacci13Gaetano Finocchiaro14and Veronica Saletti15Developmental Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, via Celoria 11, 20121 Milan, ItalyMolecular Neuro-Oncology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, via Celoria 11, 20121 Milan, ItalyMedical Genetics Unit, Woman-Child-Newborn Department, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore Policlinico, via Francesco Sforza 28, 20122 Milan, ItalyMolecular Neuro-Oncology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, via Celoria 11, 20121 Milan, ItalyMolecular Neuro-Oncology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, via Celoria 11, 20121 Milan, ItalyDevelopmental Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, via Celoria 11, 20121 Milan, ItalyDepartment of Pathophysiology and Transplantation, Pediatric Highly Intensive Care Unit, Università degli Studi di Milano, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, via Francesco Sforza 28, 20122 Milan, ItalyPaediatric Neurology and Neuromuscular Disorders, University of Genoa and Istituto Giannina Gaslini, Via Gerolamo Gaslini 5, 16147 Genoa, ItalyPediatric Neuropsychiatry, Spedali Civili of Brescia, Piazzale Spedali Civili 1, 25125 Brescia, ItalyPediatric Department, ASST Grande Ospedale Metropolitano Niguarda, Piazza Ospedale Maggiore 3, 20162 Milan, ItalyNeuroradiology Department, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, via Francesco Sforza 28, 20122 Milan, ItalyNeuroradiology Department, Fondazione IRCCS Istituto Neurologico Carlo Besta, via Celoria 11, 20121 Milan, ItalyDevelopmental Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, via Celoria 11, 20121 Milan, ItalyMedical Genetics Unit, Woman-Child-Newborn Department, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore Policlinico, via Francesco Sforza 28, 20122 Milan, ItalyMolecular Neuro-Oncology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, via Celoria 11, 20121 Milan, ItalyDevelopmental Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, via Celoria 11, 20121 Milan, ItalyThe occurrence of optic pathway gliomas (OPGs) in children with neurofibromatosis type 1 (NF1) still raises many questions regarding screening and surveillance because of the lack of robust prognostic factors. Recent studies of an overall cohort of 381 patients have suggested that the genotype may be the main determinant of the development of OPG, with the risk being higher in patients harbouring <i>NF1 </i>mutations in the 5’ tertile and the cysteine/serine-rich domain. In an attempt to confirm this hypothesis, we used strict criteria to select a large independent cohort of 309 NF1 patients with defined constitutional NF1 mutations and appropriate brain images (255 directly enrolled and 54 as a result of a literature search). One hundred and thirty-two patients had OPG and 177 did not. The association of the position (tertiles and functional domains) and type of <i>NF1</i> mutation with the development of OPG was analysed using the χ2 test and Fisher’s exact probability test; odds ratios (ORs) with 95% confidence intervals were calculated, and Bonferroni’s correction for multiple comparisons was applied; multiple logistic regression was also used to study genotype−phenotype associations further. Our findings show no significant correlation between the site/type of NF1 mutation and the risk of OPG, and thus do not support the hypothesis that certain constitutional mutations provide prognostic information in this regard. In addition, we combined our cohort with a previously described cohort of 381 patients for a total of 690 patients and statistically re-analysed the results. The re-analysis confirmed that there were no correlations between the site (tertile and domain) and the risk of OPG, thus further strengthening our conclusions.https://www.mdpi.com/2072-6694/11/12/1838key words: neurofibromatosis type 1nf1 geneoptic pathway gliomagenotype–phenotype correlations |