Prevalence of the single-nucleotide polymorphism rs11554137 (IDH1105GGT) in brain tumors of a cohort of Italian patients

Abstract

IDH mutational status is required for proper diagnosis according to the WHO criteria revised in 2016. The single nucleotide polymorphism (SNP) rs11554137 (IDH1^105GGT) at codon 105 of IDH1 has been reported in patients with several tumor types, including those with glioma. The aim of this study is to investigate the prevalence of IDH1^105GGT in a cohort of brain tumors, and its association with clinicopathologic features and IDH1 and IDH2 missense mutations. Exon 4 of IDH1 and IDH2 was analyzed in a series of brain tumors classified according to current WHO criteria. DNA from control individuals was analyzed to infer the prevalence of IDH1^105GGT in the reference population. Analysis was performed using next generation sequencing. IDH1^105GGT was three times more frequent in patients with tumors (44/293 cases, 15.0%) vs. population controls (6/109, 5.5%) (p = 0.0102). IDH1^105GGT was more frequent in grade III tumors (26.1%) compared to grade II (10.9%, p = 0.038) and grade IV tumors (13.7%, p = 0.041). IDH1 ^105GGT was more frequent in grade II and III tumors without an IDH tumor missense mutation (43.8%) than in those with (11.5%, p = 0.005). The IDH1^105GGT SNP likely represents an important genetic marker, worthy of additional investigation to better understand the clinical and biological features of IDH-WT infiltrating gliomas.

Figure 1

Prevalence of IDH^105GGT. (A) Comparison of IDH^105GGT between controls and patients with brain tumors. (B) IDH^105GGT in grade II, III and IV brain tumors. (C) IDH^105GGTin gliomas with and without IDH tumor missense mutation. (D) IDH^105GGT in grade II and III gliomas with and without IDH tumor missense mutation and in grade IV without IDH tumor missense mutation. IDH^105GGT: cases with IDH^105GGT; No-IDH^105GGT: cases without the IDH^105GGT; GII: grade II brain tumors; GIII: grade III brain tumors; GIV: grade IV brain tumors; GBM: glioblastoma; R132: cases with IDH-missense mutation; WT: wild type.

Figure 2

Age distribution of patients according to the presence of IDH1^105GGT and IDH missense tumor mutations. IDH1^105GGT: patients with tumor with IDH1^105GGT; IDH1^105WT: patients with tumor without IDH1^105GGT; IDHmut: patients with tumor with IDH missense mutation; IDHWT: patients with tumor without IDH missense mutation. *p < 0.05 (Tukey’s multiple comparisons test); ***p < 0.001 (Tukey’s multiple comparisons test). Bars represent standard deviation (SD).