International Medical Case Reports Journal (Apr 2020)
Adamantinomatous Craniopharyngioma in an Adult: A Case Report with NGS Analysis
Abstract
Raid A Jastania,1 Muhammad Saeed,2,3 Hisham Al-Khalidi,4 Khalid AlQuthami,5 Tahani H Nageeti,6 Faisal A Al-Allaf,7,8 Kristoffer Valerie,9 Mohiuddin M Taher7,8 1Department of Pathology, Faculty of Medicine, Umm-Al-Qura University, Makkah, Saudi Arabia; 2Department of Radiology, Faculty of Medicine, Umm-Al-Qura University, Makkah, Saudi Arabia; 3Department of Radiology, Al-Noor Specialty Hospital, Makkah, Saudi Arabia; 4Department of Pathology, King Saud University, Riyadh, Saudi Arabia; 5Division of Histopathology, Department of Laboratory Medicine and Blood Bank, Al-Noor Specialty Hospital, Makkah, Saudi Arabia; 6Department of Radiation Oncology, King Abdullah Medical City, Makkah, Saudi Arabia; 7Science and Technology Unit, Umm-Al-Qura University, Makkah, Saudi Arabia; 8Department of Medical Genetics, Faculty of Medicine, Umm-Al-Qura University, Makkah, Saudi Arabia; 9Department of Radiation Oncology and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USACorrespondence: Mohiuddin M Taher Email [email protected]: 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.Keywords: craniopharyngioma, adamantinomatous, brain tumor, NGS, next generation DNA sequencing, CTNNB1
