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Case Reports
. 2021 Dec 16:11:739309.
doi: 10.3389/fonc.2021.739309. eCollection 2021.

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

Xing Guo  1   2 , Teng Chen  1   2 , Shiming Chen  3 , Chao Song  4 , Dezhi Shan  1   2 , Shujun Xu  1   2 , Shuo Xu  1   2
Affiliations
Case Reports

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

Xing Guo et al. Front Oncol. .

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.

Keywords: FGFR2; TERT; amplification; gene fusion; glioblastoma; somatic variation.

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Conflict of interest statement

Author SC was employed by Jiangsu Simcere Diagnostics Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Pre-operative T2-weighted (A), T2-FLAIR weighted (B), and enhanced axial, coronal, sagittal T1-weighted (C, D) magnetic resonance images showed a heterogeneously enhancing solid mass in pineal gland region, extending into the bilateral thalamus and obliterating the third ventricle, with ventriculomegaly. A flow chart showcased the timeline with relevant data from the episode of care (E).
Figure 2
Figure 2
H&E-stained sections showed the tumor was comprised of atypical glial tumor cells with vascular proliferation and necrosis (A). Mitotic figures and perivascular pseudorosettes were easily identified (B). Immunohistochemical sections presented positive expression of P53 (C, ZM-0408, ZSGB−BIO), CD99 (D, ZM-0296, ZSGB−BIO), GFAP (E, MXB Biotechnologies), Syn (F, ZA-0506, ZSGB-BIO), Olig-2 (G, ZA-0561, ZSGB-BIO), IDH1 (H, ZM-0447, ZSGB-BIO) and negative expression of ATRX (J, ZA-0016, ZSGB-BIO) in the tumor. The Ki-67 proliferative index was 30–40% (I, H10501, Ventata). In addition, TERT (K, TA301588, ZSGB-BIO) was substantially expressed in the tumor.
Figure 3
Figure 3
Copy number variation (CNV) of the TERT gene was high in the whole genome (A). TERT gene was amplified 8.94-fold on chromosome 5 (A). Next generation sequencing (NGS) revealed significant TERT gene rearrangement (B), including multiple TERT (Exon16-2)–NUBPL (Exon4-11) (C), MARCH6 (Exon1-25)–TERT (Intergenic) (D), and CJD4 (Intergenic)–TERT (Exon10-16) (E) fusions.
Figure 4
Figure 4
Next generation sequencing (NGS) revealed significant FGFR2 gene rearrangement (A), including multiple CXCL17 (Intergenic)–FGFR2 (Exon16-18) (B), SIPA1L3 (Exon1-4)–FGFR2 (Exon16-18) (C), FGFR2 (Exon1-16)–SIPA1L3 (Exon4-1) (D) and FGFR2 (Exon1-16)–CEACAM1 (Intergenic) (E) fusions.
See this image and copyright information in PMC

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