Page 82 - Molecular features of low-grade developmental brain tumours

gene-CpG
P-value
R
3
CHAPTER 3
Table 3. Correlations between SEGA1 or SEGA2 unique genes and their corresponding CpGs.
MFAP5-cg07708516 MFAP5-cg15815843 MFAP5-cg18574995 SLC15A2-cg10523671 GPT2-cg05380921 CLCC1-cg05048348 CYP4F12-cg04608829 KLHL33-cg10982443 C12orf29-cg02981078 SELENBP1-cg24486037 MTERFD1-Cg16177163_1 ICAM2-cg24080793 CHD7-cg20078807
0,000530223 0,000620988 0,00145419 0,025167117 0,038992623 0,034586058 0,007203143 0,019586595 0,005023238 0,00731857 0,03252444 0,025167117 0,020516043
-0,824175824 -0,818681319 -0,785714286 -0,615384615 -0,576923077 -0,587912088 -0,704264765 -0,635488909 -0,725274725 -0,703296703 -0,593406593 -0,615384615 -0,631868132
80
Interestingly, we identified two subgroups (SEGA1 and SEGA2) in the SEGA methylation data with one group subdviding further into two smaller groups. These two groups are distinct in the methylation of genes related to the adaptive immune response and the MAPK cascade. However, no correlation was found between the methylation and RNA expression of these specific genes. Due to the complexity of RNA expression regulation, the effect of methylation changes might not be directly reflected in the RNA expression data. Higher expression of the T cell marker CD3 was found in SEGA2 compared to SEGA1 confirming differences in the adaptive immune response between the two groups. It could be possible that these methylation subgroups reflect differences in inflammatory cell content. However, it must be noted that the differences are small and only detectible with quantification. The MAPK pathway has been shown to be an important pathway for SEGA growth and has been suggested as a novel target for therapy for patients with SEGA 16,18,50. Therefore, the differences in methylation of this pathway between the two groups found in this study is interesting and could potentially reflect how these tumours would respond to MAPK inhibitors. Since MAPK inhibitors are not routinely used for SEGA treatment this could not be evaluated within this study. Furthermore, none of the clinical data available could explain the subgroups found. It is very well possible that these two groups do reflect other important clinical features that were not evaluated in this study, such as tumour progression. Moreover, since the majority of patients included were not treated with mTOR inhibitors, it cannot be excluded that the biological make up of these subgroups reflect potential response to mTOR inhibitors. Therefore, DNA methylation analysis on SEGAs in retrospective studies are highly needed in order to unravel the clinical relevance of these subgroups.