Case Report: Identification of Multiple TERT and FGFR2 Gene Fusions in a Pineal Region Glioblastoma Case

Abstract

As an oncogenic somatic variant, telomerase reverse transcriptase promoter (TERTp) mutations are frequently observed in adult glioblastoma (GBM). Alternatively, we report the first case of glioblastoma with TERT amplification accompanied by multiple TERT and FGFR2 gene fusions instead of TERTp mutation. A 55-year-old woman presented with dizziness, headache, and diplopia for three weeks. Magnetic resonance imaging (MRI) demonstrated a heterogeneously enhancing lobulated mass centered in the pineal region. Partial tumor resection and ventriculoperitoneal shunt were achieved, and the residual tumor was then treated with standard radiation. The tumor was diagnosed as GBM, IDH-wild type, WHO grade IV, and the Ki67 proliferation index was high (30–40%). Intriguingly, TERT amplification without TERTp mutation was identified via next generation sequencing (NGS). Further analysis revealed multiple TERT (TERT–NUBPL, MARCH6–TERT, and CJD4–TERT) and FGFR2 (CXCL17–FGFR2, SIPA1L3–FGFR2, FGFR2–SIPA1L3, and FGFR2–CEACAM1) gene fusions. After the surgery, the patient’s condition deteriorated rapidly due to the malignant nature of the tumor and she died with an overall survival of 3 months. Our report provides the molecular clue for a novel telomerase activation and maintenance mechanism in GBM.

Long-Term Survival of Patients With Glioblastoma of the Pineal Gland: A ChatGPT-Assisted, Updated Case of a Multimodal Treatment Strategy Resulting in Extremely Long Overall Survival at a Site With Historically Poor Outcomes

“…We previously reported the median survival of six months (range, 2-24 months) for pineal glioblastoma [ 1 ]. The available data in the cases published after 2017 [ 3 - 6 ] have similarly demonstrated a median survival of six months (range, 3-7 months). Excluding the present case, the median survival of all current cases in the literature stands at six months (range, 2-24 months).…”

“…A fourth case report detailed a 55-year-old female patient who was admitted to the hospital for dizziness, headache, blurred and double vision [ 6 ]. The physical examination revealed Parinaud syndrome, and an MRI confirmed a heterogeneously enhancing mass in the midline pineal region with ventriculomegaly.…”

The Relevance of Telomerase and Telomere-Associated Proteins in B-Acute Lymphoblastic Leukemia

“…Similarly, c -MYC promotes hTERT deregulation, resulting in the reduction of telomere length, telomerase activity and cell proliferation [ 82 ]. Additionally, TERT can act as a transcription co-factor that regulates expression of several genes [ 77 ], which are summarized in Supplementary Table S1 [ 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 ,…”