Abstract
The proto-oncogene tyrosine-protein kinase ROS1 (ROS1) is a tyrosine kinase that is closely related to anaplastic lymphoma kinase receptor (ALK). We describe a novel KLC1–ROS1 fusion identified in a case of pediatric low-grade glioma. This was detected by RNA sequencing and confirmed by reverse-transcription PCR and fluorescent in situ hybridization. Immunohistochemical staining for ROS1 was positive in the tumor cytoplasm. In vitro analysis demonstrated the oncogenic activity of this fusion, which was suppressed by the ALK/ROS1 inhibitor, crizotinib. Our case and others suggest that various ROS1 fusions might be present in a subset of pediatric gliomas, which could be targeted for therapy.
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References
Davies KD, Doebele RC (2013) Molecular pathways: ROS1 fusion proteins in cancer. Clin Cancer Res 19:4040–4045
Uguen A, De Braekeleer M (2016) ROS1 fusions in cancer: a review. Future Oncol 12:1911–1928
Lim SM, Choi J, Chang JH et al (2015) Lack of ROS1 gene rearrangement in glioblastoma multiforme. PLoS One 10:e0137678
Verhey KJ, Hammond JW (2009) Traffic control: regulation of kinesin motors. Nat Rev Mol Cell Biol 10:765–777
Togashi Y, Soda M, Sakata S et al (2012) KLC1-ALK: a novel fusion in lung cancer identified using a formalin-fixed paraffin-embedded tissue only. PLoS One 7:e31323
Wang P, Xiao P, Ye Y et al (2017) Rapid response of brain metastasis to crizotinib in a patient with KLC1-ALK fusion and MET gene amplification positive non-small cell lung cancer: a case report. Cancer Biol Med 14:183–186
Johnson A, Severson E, Gay L et al (2017) Comprehensive genomic profiling of 282 pediatric low- and high-grade gliomas reveals genomic drivers, tumor mutational burden, and hypermutation signatures. Oncologist 22:1478–1490
Coccé MC, Mardin BR, Bens S et al (2016) Identification of ZCCHC8 as fusion partner of ROS1 in a case of congenital glioblastoma multiforme with a t(6;12)(q21;q24.3). Genes Chromosomes Cancer 55:677–687
Olsen TK, Panagopoulos I, Meling TR et al (2015) Fusion genes with ALK as recurrent partner in ependymoma-like gliomas: a new brain tumor entity? Neuro Oncol 17:1365–1373
Aghajan Y, Levy ML, Malicki DM et al (2016) Novel PPP1CB-ALK fusion protein in a high-grade glioma of infancy. BMJ Case Rep. https://doi.org/10.1136/bcr-2016-217189
Kiehna EN, Arnush MR, Tamrazi B et al (2017) Novel GOPC(FIG)-ROS1 fusion in a pediatric high-grade glioma survivor. J Neurosurg Pediatr 20:51–55
Rossing M, Yde CW, Sehested A et al (2017) Genomic diagnostics leading to the identification of a TFG-ROS1 fusion in a child with possible atypical meningioma. Cancer Genet 212–213:32–37
Cameron L, Solomon B (2015) New treatment options for ALK-rearranged non-small cell lung cancer. Curr Treat Options Oncol 16:49
Bubendorf L, Büttner R, Al-Dayel F et al (2016) Testing for ROS1 in non-small cell lung cancer: a review with recommendations. Virchows Arch 469:489–503
Yoshida A, Tsuta K, Wakai S et al (2014) Immunohistochemical detection of ROS1 is useful for identifying ROS1 rearrangements in lung cancers. Mod Pathol 27:711–720
Fujita H, Yoshida A, Taniguchi H et al (2015) Adult-onset inflammatory myofibroblastic tumour of the stomach with a TFG-ROS1 fusion. Histopathology 66:610–612
Yamamoto H, Yoshida A, Taguchi K et al (2016) ALK, ROS1 and NTRK3 gene rearrangements in inflammatory myofibroblastic tumours. Histopathology 69:72–83
Acknowledgements
The authors thank the patient and their family for participating in this research. We thank T. Ushijima, S. Yamashita, and R. Nagano for their advice and technical support for DNA analysis. This work was supported in part by the Practical Research for Innovative Cancer Control from Japan Agency for Medical Research and Development, AMED [no. JP17ck0106168 (T.K. and K. I.)].
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Nakano, Y., Tomiyama, A., Kohno, T. et al. Identification of a novel KLC1–ROS1 fusion in a case of pediatric low-grade localized glioma. Brain Tumor Pathol 36, 14–19 (2019). https://doi.org/10.1007/s10014-018-0330-3
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DOI: https://doi.org/10.1007/s10014-018-0330-3