Glioblastomas harboring gene fusions detected by next-generation sequencing
- PDF / 729,012 Bytes
- 9 Pages / 595.276 x 790.866 pts Page_size
- 4 Downloads / 214 Views
ORIGINAL ARTICLE
Glioblastomas harboring gene fusions detected by next‑generation sequencing Ha Young Woo1 · Kiyong Na2 · Jihwan Yoo3 · Jong Hee Chang3 · Young Nyun Park1 · Hyo Sup Shim1 · Se Hoon Kim1 Received: 16 July 2020 / Accepted: 31 July 2020 © The Japan Society of Brain Tumor Pathology 2020
Abstract Oncogenic gene fusions have been reported in diffuse gliomas and may serve as potential therapeutic targets. Here, using next-generation sequencing analysis (Illumina TruSight Tumor 170 panel), we analyzed a total of 356 diffuse gliomas collected from 2017 to 2019 to evaluate clinical, pathological, and genetic features of gene fusion. We found 53 cases of glioblastomas harboring the following oncogenic gene fusions: MET (n = 18), EGFR (n = 14), FGFR (n = 12), NTRK (n = 5), RET (n = 2), AKT3 (n = 1), and PDGFRA fusions (n = 1). Gene fusions were consistently observed in both IDH-wildtype and IDH-mutant glioblastomas (8.8% and 9.4%, p = 1.000). PTPRZ1–MET fusion was the only fusion that genetically resembled secondary glioblastomas (i.e., high frequency of IDH mutation, ATRX loss, TP53 mutation, and absence of EGFR amplification), whereas other gene fusion types were similar to primary glioblastomas (i.e., high frequency of IDH-wildtype, TERT mutation, EGFR amplification, and PTEN mutation). In IDH-wildtype glioblastoma patients, multivariable analysis revealed that the PTPRZ1–MET fusion was associated with poor progression-free survival (HR [95% CI]: 5.42 (1.72–17.05), p = 0.004). Additionally, we described two novel cases of CCDC6–RET fusion in glioma. Collectively, our findings indicate that targetable gene fusions are associated with aggressive biological behavior and can aid the clinical treatment strategy for glioma patients. Keywords Next-generation sequencing · Glioma · Fusion · Glioblastoma · MET
Introduction Gene fusions are hybrid genes formed by the combination of the DNA sequences of two genes. Gene fusions have the potential to create chimeric proteins with altered functions. Recently, a large-scale study reported that fusion events drive tumor development in 16.5% of malignant tumors and function as the sole driver in more than 1% of them [1]. Although most fusion events appear to be passenger * Se Hoon Kim [email protected] 1
Department of Pathology, Yonsei University College of Medicine, 50‑1, Yonsei‑Ro, Seodaemun‑gu, Seoul 03722, South Korea
2
Department of Pathology, Kyung Hee University Hospital, 26 Kyungheedae‑Ro, Dongdaemun‑gu, Seoul 02447, South Korea
3
Department of Neurosurgery, Yonsei University College of Medicine, 50‑1, Yonsei‑Ro, Seodaemun‑gu, Seoul 03722, South Korea
mutations, some are predicted to play important roles in tumor development and progression [2–4]. For example, gene fusions drive the majority of lymphomas and leukemias [5], and the EML4–ALK fusion causes a transformation in non-small cell lung cancer [6]. Notably, precise fusion gene diagnosis can also aid in therapeutics, with several drugs having been developed to prevent the formation of gene fusions
Data Loading...
