TY - JOUR
T1 - Risk of optic pathway glioma in neurofibromatosis type 1
T2 - No evidence of genotype–phenotype correlations in a large independent cohort
AU - Melloni, Giulia
AU - Eoli, Marica
AU - Cesaretti, Claudia
AU - Bianchessi, Donatella
AU - Ibba, Maria Cristina
AU - Esposito, Silvia
AU - Scuvera, Giulietta
AU - Morcaldi, Guido
AU - Micheli, Roberto
AU - Piozzi, Elena
AU - Avignone, Sabrina
AU - Chiapparini, Luisa
AU - Pantaleoni, Chiara
AU - Natacci, Federica
AU - Finocchiaro, Gaetano
AU - Saletti, Veronica
PY - 2019/12
Y1 - 2019/12
N2 - 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 NF1 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 NF1 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.
AB - 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 NF1 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 NF1 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.
KW - Genotype
KW - Neurofibromatosis type 1
KW - NF1 gene
KW - Optic pathway glioma
KW - Phenotype correlations
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U2 - 10.3390/cancers11121838
DO - 10.3390/cancers11121838
M3 - Article
AN - SCOPUS:85075284497
VL - 11
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 12
M1 - 1838
ER -