<p>Adamantinomatous Craniopharyngioma in an Adult: A Case Report with NGS Analysis</p>

Abstract

Purpose: Several recent studies have documented CTNNB1 and BRAF mutations which are mutually exclusive for adamantinomatous craniopharyngioma (ACP) and papillary craniopharyngioma (PCP) tumors. This discovery is helpful in the development of novel targeted therapies in successful clinical trials with BRAF mutations in PCP cases. However, no such targeted therapy is available yet for ACP. Here, we report novel mutations, which are not previously reported, in a case of an adult ACP using NGS analysis. Results: Patient DNA was sequenced using Ion PI v3 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 in c.101G>T; in TP53 a known missense mutation in c.215C>G; and two known missense variants in PIK3CA, viz., in c.1173A>G; in exon 7, and in c.3128T>C; in exon 21, were found, respectively. Seven synonymous mutations were detected in this tumor, viz., in IDH1 (rs11554137), in FGFR3 (rs7688609), in PDGFRA (rs1873778), in APC (COSM3760869), in EGFR (rs1050171), in MET (rs35775721), and in RET (rs1800861), respectively. Three known, intronic variants were found in genes, such as PIK3CA, KDR, and JAK3, respectively. Also, a 3'-UTR and a splice site acceptor site variant in CSF1R and FLT3 genes were found in this tumor. We have shown allele coverage, allele ratio, and p-value, for all these mutations. The p-values and Phred quality score were significantly high for these variants. Conclusion: As reported in previous studies, in ACP tumors we found a CTNNB1 mutation by NGS analysis. The PIK3CA variants we detected were not known previously in ACP tumors. Finding the PIK3CA mutations in the ACP tumors may help develop targeted therapy for a subset of craniopharyngiomas with PIK3CA activating mutations. Clinical trials are in progress with specific PIK3CA inhibitors in advanced stages of many cancers.

Determination of TMPRSS2‐ERG, SPOP, FOXA1, and IDH1 prostate cancer molecular subtypes in Colombian patients and their possible implications for prognosis

“…This SNP is located in the same exon as the R132 mutations and has been reported previously in other types of cancer such as gliomas, glioblastomas, brain tumors, astrocytoma, craniopharyngioma and acute myeloid leukemia in pediatric and adult population, and has been associated with a negative prognosis in some of these neoplasms (Accetta et al, 2018; Acquaviva et al, 2018; Jastania et al, 2020; Soyer et al, 2017; X. W. Wang et al, 2013). The influence of SNP on the enzyme function had been associated with an increase in mRNA‐level expression, affecting intracellular NAPH levels (Acquaviva et al, 2018; Komar, 2007).…”

Supratentorial Sporadic Hemangioblastoma: A Case Report With Mutation Profiling Using Next-Generation DNA Sequencing

“…The HBL tumor of this study exhibited exon 25 and exon 9 mutations in ALK and FGFR3 genes (Table 3 ); however, mutations in exon 29 and exon 16 in these two genes were previously reported in an atypical-choroid plexus papilloma (a-CPP) tumor [ 21 ]. In the ALK gene, exon 25 contained a c.3750T>G; p. (Ile1250Met) mutation in the HBL tumor in the present study, and another variant (COSM10044698) was reported at this site, c.3748 A>G; p. (Ile1250Val).…”

“…Details of histopathological and immunological methods were published by us previously [ 20 , 21 ]. The formalin-fixed paraffin-embedded (FFPE) tumor tissue used in this NGS analysis was obtained from the Al-Noor Specialty Hospital, Makkah.…”

A Rare Case of Adamantinomatous Craniopharyngioma in an Adult

“…ACPs are extremely rare in adults, with most adult cases presenting over 50 years of age [9,10]. As the distribution of these tumors follows a bimodal curve, the age at diagnosis for our patient makes this case even more unique.…”