Adamantinomatous Craniopharyngioma in an Adult: A case report with NGS analysis

Several recent studies have documented CTNNB1 and BRaf mutations which are mutually exclusive for adamantinomatous craniopharyngioma and papillary craniopharyngioma tumors. This discovery is helping in development of novel targeted therapies in successful clinical trials with BRaf mutations in papillary craniopharyngioma cases. However, no such targeted therapy is available yet for adamantinomatous craniopharyngioma. Here, we report new mutations which are not previously reported in a case of an adult adamantinomatous craniopharyngioma using NGS analysis.Patient DNA was sequenced using Ion PI chip on Ion Proton. A total of 16 variants were identified in this tumor by NGS analysis, out of which four were missense mutations, seven were synonymous mutations, and five were intronic variants. In CTNNB1 gene a known missense mutation and in TP53 gene a missense mutation and two known missense variants in PIK3CA, in exon 7, and in exon 21, were found respectively. Seven synonymous mutation were detected in this tumor such as in IDH1, FGFR3, PDGFRA, APC, EGFR, MET, and in RET genes respectively. Three known, intronic variants were found in genes such as, PIK3CA, KDR, and JAK3 respectively. Also, an UTR and a splice site acceptor site variant in CSF1R and FLT3 genes were found in this tumor. We have shown for each target, allele coverage, allele ratio, p-value, for these mutations. The p-values and Phred quality score was significantly high for these variants.As reported in previous studies in adamantinomatous craniopharyngioma tumors we found a CTNNB1 mutation by NGS analysis. The PIK3CA variants we detected were not known previously in this tumor. Finding the PIK3CA mutations in the adamantinomatous craniopharyngioma tumors may help to develop targeted therapy for a subset of craniopharyngiomas with PIK3CA activating mutations. Clinical trials are being in progress with specific PIKCA3 inhibitors in advanced stages of many cancers.