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. 2017 Sep 22;3(5):e192.
doi: 10.1212/NXG.0000000000000192. eCollection 2017 Oct.

Children with 5'-end NF1 gene mutations are more likely to have glioma

Corina Anastasaki  1 , Stephanie M Morris  1 , Feng Gao  1 , David H Gutmann  1
Affiliations

Children with 5'-end NF1 gene mutations are more likely to have glioma

Corina Anastasaki et al. Neurol Genet. .

Abstract

Objective: To ascertain the relationship between the germline NF1 gene mutation and glioma development in patients with neurofibromatosis type 1 (NF1).

Methods: The relationship between the type and location of the germline NF1 mutation and the presence of a glioma was analyzed in 37 participants with NF1 from one institution (Washington University School of Medicine [WUSM]) with a clinical diagnosis of NF1. Odds ratios (ORs) were calculated using both unadjusted and weighted analyses of this data set in combination with 4 previously published data sets.

Results: While no statistical significance was observed between the location and type of the NF1 mutation and glioma in the WUSM cohort, power calculations revealed that a sample size of 307 participants would be required to determine the predictive value of the position or type of the NF1 gene mutation. Combining our data set with 4 previously published data sets (n = 310), children with glioma were found to be more likely to harbor 5'-end gene mutations (OR = 2; p = 0.006). Moreover, while not clinically predictive due to insufficient sensitivity and specificity, this association with glioma was stronger for participants with 5'-end truncating (OR = 2.32; p = 0.005) or 5'-end nonsense (OR = 3.93; p = 0.005) mutations relative to those without glioma.

Conclusions: Individuals with NF1 and glioma are more likely to harbor nonsense mutations in the 5' end of the NF1 gene, suggesting that the NF1 mutation may be one predictive factor for glioma in this at-risk population.

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Figures

Figure 1
Figure 1. Distribution of NF1 gene mutations in neurofibromatosis type 1 participants with and without glioma
(A) Histogram indicating the location of NF1 gene mutations identified in participants with glioma (n = 101; black bars) or without glioma (n = 209; gray bars). The different regions of the NF1 gene are highlighted below the exons (5′ end: exons 1–26 and 3′ end: exons 27–57, including the RAS-GAP domain). The specificity, sensitivity, and unadjusted odds ratio (OR) for glioma in participants with any NF1 gene mutation are shown in the table above the graph. (B) Summary of the combined weighted OR after sensitivity meta-analysis (n = 296 patients). CI = confidence interval; WUSM = Washington University School of Medicine.
Figure 2
Figure 2. Specificity, sensitivity, and odds ratios for glioma in participants with neurofibromatosis type 1 and nonsense or truncating NF1 gene mutations
(A) Summary of the specificity, sensitivity, and unadjusted odds ratio (OR) for glioma in participants with nonsense mutations in the 5′ end of the NF1 gene (exons 1–26). (B) Summary of the combined weighted OR for glioma after sensitivity meta-analysis (n = 73 patients). (C) Summary of the specificity, sensitivity, and unadjusted OR for glioma in participants with truncating mutations in the 5′ end of the NF1 gene (exons 1–26). (D) Summary of the combined weighted OR for glioma after sensitivity meta-analysis (n = 193). CI = confidence interval; WUSM = Washington University School of Medicine.
See this image and copyright information in PMC

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