ROS1 Alterations as a Potential Driver of Gliomas in Infant, Pediatric, and Adult Patients

Meredith, David M.; Cooley, Linda D.; Dubuc, Adrian M.; Morrissette, Jennifer J.D.; Sussman, Robyn T.; Nasrallah, MacLean P.; Rathbun, Pamela; Yap, Kai Lee; Wadhwani, Nitin R.; Bao, Liming; Wolff, Daynna J.; Ida, Cristiane M.; Sukhanova, Madina; Horbinski, Craig; Jennings, Lawrence J.; Farooqi, Midhat S.; Gener, Melissa; Ginn, Kevin; Kam, Kwok Ling; Sasaki, Koji; Kanagal‐Shamanna, Rashmi; Alexandrescu, Sanda; Brat, Daniel J.; Lu, Xinyan

doi:10.1016/j.modpat.2023.100294

Cited by 4 publications

(1 citation statement)

References 44 publications

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“…22 23 25 In a recent multi-institutional study, however, ROS1 fusions in glioma were identified beyond the age range, with GOPC being the most frequent partner (77%) across all age groups, although (unlike our case) the infantile tumours were uniformly high grade. 44 The identification of pathognomonic potentially targetable fusions in infantile cases is particularly helpful in view of the diagnostic and therapeutic challenges and paradoxical survival profiles in this age group. 24 Responses to specific TRK inhibitors (eg, crizotinib) have been reported but further validation is needed.…”

Section: Original Researchmentioning

confidence: 99%

Clinicopathological analysis of BRAF and non-BRAF MAPK pathway-altered gliomas in paediatric and adult patients: a single-institution study of 40 patients

Ali,

Almanabri,

Ali

et al. 2024

J Clin Pathol

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AimsMitogen-activated protein kinase (MAPK) pathway alteration is a major oncogenic driver in paediatric low-grade gliomas (LGG) and some adult gliomas, encompassing BRAF (most common) and non-BRAF alterations. The aim was to determine the frequency, molecular spectrum and clinicopathological features of MAPK-altered gliomas in paediatric and adult patients at our neuropathology site in Kuwait.MethodsWe retrospectively searched the data of molecularly sequenced gliomas between 2018 and 2023 for MAPK alterations, revised the pathology in view of the 2021 WHO classification and evaluated the clinicopathological data for possible correlations.ResultsOf 272 gliomas, 40 (15%) harboured a MAPK pathway alteration in 19 paediatric (median 9.6 years; 1.2–17.6) and 21 adult patients (median 37 years; 18.9–89.2), comprising 42% and 9% of paediatric and adult cases, respectively. Pilocytic astrocytoma and glioblastoma were the most frequent diagnoses in children (47%) and adults (43%), respectively. BRAF V600E (n=17, 43%) showed a wide distribution across age groups, locations and pathological diagnoses while KIAA1549::BRAF fusion (n=8, 20%) was spatially and histologically restricted to cerebellar paediatric LGGs. Non-V600E variants and BRAF amplifications accompanied other molecular aberrations in high-grade tumours. Non-BRAF MAPK alterations (n=8) included mutations and gene fusions involving FGFR1, NTRK2, NF1, ROS1 and MYB. Fusions included KANK1::NTRK2, GOPC::ROS1 (both infant hemispheric gliomas), FGFR1::TACC1 (diffuse LGG), MYB::QKI (angiocentric glioma) and BCR::NTRK2 (glioblastoma). Paradoxical H3 K27M/MAPK co-mutations were observed in two LGGs.ConclusionThe study provided insights into MAPK-altered gliomas in Kuwait highlighting the differences among paediatric and adult patients and providing a framework for planning therapeutic polices.

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Section: Original Researchmentioning

confidence: 99%

Clinicopathological analysis of BRAF and non-BRAF MAPK pathway-altered gliomas in paediatric and adult patients: a single-institution study of 40 patients

Ali,

Almanabri,

Ali

et al. 2024

J Clin Pathol

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Molecular-targeted therapy for childhood low-grade glial and glioneuronal tumors

Siegel,

Duke,

Kilburn

et al. 2024

Childs Nerv Syst

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Prolonged response to entrectinib in an adult patient with recurrent glioblastoma harboring a GOPC::ROS1 fusion

Cerretti,

Padovan,

Guerriero

et al. 2024

Neuro-Oncology Advances

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Introductory paragraph Data on the use of targeted therapies in glioma are still limited and the identification of useful targetable mutations is still under investigation. Among all the relevant alterations identified through next generation sequencing (NGS) tests, ROS1 alterations can rarely be found in gliomas, and the most common of them is GOPC::ROS1 fusion. Targeted therapies, such as entrectinib, are available for such alterations. Hereby, the case of a patient affected by GOPC::ROS1 fused glioblastoma and treated with entrectinib is presented; this patient achieved a complete and prolonged response with no relevant toxicities from the treatment.

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ROS1 Alterations as a Potential Driver of Gliomas in Infant, Pediatric, and Adult Patients

Cited by 4 publications

References 44 publications

Clinicopathological analysis of BRAF and non-BRAF MAPK pathway-altered gliomas in paediatric and adult patients: a single-institution study of 40 patients

Clinicopathological analysis of BRAF and non-BRAF MAPK pathway-altered gliomas in paediatric and adult patients: a single-institution study of 40 patients

Molecular-targeted therapy for childhood low-grade glial and glioneuronal tumors

Prolonged response to entrectinib in an adult patient with recurrent glioblastoma harboring a GOPC::ROS1 fusion

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