Project description:The present study aimed to determine genomic changes in sporadic intracranial hemangioblastoma (HBL), and the mutation patterns were analyzed using next-generation DNA sequencing (NGS). In this NGS analysis of the HBL tumor, 67 variants of 41 genes were identified. Of these, 64 were single-nucleotide variants (SNVs), two were exonic insertions and deletions (INDEL), and one was an intronic INDEL. In total, 15 were missense exonic variants, including an insertion variant in the NRAS gene, c.1_2insA, and a deletion variant, c.745delT, in the HNF1A gene, both of these mutations produced a termination codon. Other exonic missense variants found in the tumor were CTNNB1, FGFR3, KDR, SMO, HRAS, RAI1, and a TP53 variant (c.430C>G). Moreover, the results of the present study revealed a novel variant, c.430C>G, in TP53 and two missense variants of SND1 (c.1810G>C and c.1814G>C), which were also novel. ALK (rs760315884) and FGFR2 (rs1042522) missense variants were reported previously. Notably, a total of 10 previously reported single-nucleotide polymorphisms (SNPs) were found in this tumor in genes including MLH1 (rs769364808), FGFR3 (rs769364808), two variants (rs1873778 and rs2228230) in PDGFRA, KIT (rs55986963), APC (rs41115), and RET (rs1800861). The results of this study revealed a synonymous mutation (SNP) in c.1104 G>T; p. (Ser368Ser) in the MLH1 gene. In this amino acid (AA) codon, two other variants are also known to cause missense substitutions, c.1103C>G; p. (Ser368Trp); COSM6986674) and c.1103C>T; p.(Ser368Leu; COSM3915870), were found in hematopoietic and urinary tract tissue, respectively. However, three SNPs found in genes such as ALK, KDR, and ABL1 in the HBL tumor in this study were not reported in UCSC, COSMIC, and ClinVar databases. Additionally, 19 intronic variants were identified in this tumor. One intronic SNV was present in each of the following genes: EGFR, ERBB4, KDR, SMO, CDKN2B, PTEN, PTPN11, RB1, AKT1, and ERBB2. In PIK3CA and FBXL18 genes, two intronic variants were present, and in the SND1 gene, three intronic variants were detected in the HBL tumor presented in this study. Notably, only one of these was reported in the catalog of somatic mutations in cancer. Only one 3'-untranslated region (UTR) insertion variant in the NRAS gene (c.*2010T>AT) was detected in the tumor of the present study, and this was a splice site acceptor. A TP53 intronic mutation (c.782+1G>T) was the only pathogenic splice_donor_variant found in this HBL tumor. The frequency of variants and Phred scores were markedly high, and the p-values were significant for all of the aforementioned mutations. In summary, a total of 15 missense, 10 synonymous, and 19 intronic variants were identified in the HBL tumor. Results of the present study detected one novel insertion in NRAS and one novel deletion in HNF1A genes, a novel missense variant in the TP53 gene, and two novel missense variants of SND1. Hotspot mutations in other cancer driver genes, such as PTEN, ATM, SMAD4, SMARCB1, STK11, NPM1, CDKN2A, and EGFR, which are frequently affected in gliomas, were not found in the tumor of the present study. Future studies should aim to validate oncogenic mutations that may act as novel targets for the treatment of these tumors.
| S-EPMC10233511 | biostudies-literature
