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Clinical management and genomic profiling of pediatric low-grade gliomas in Saudi Arabia

Pediatric Low Grade Gliomas (PLGGs) display heterogeneity regarding morphology, genomic drivers and clinical outcomes. The treatment modality dictates the outcome and optimizing patient management can be challenging. In this study, we profiled a targeted panel of cancer-related genes in 37 Saudi Ara...

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Autores principales: Mobark, Nahla A., Alharbi, Musa, Alhabeeb, Lamees, AlMubarak, Latifa, Alaljelaify, Rasha, AlSaeed, Mariam, Almutairi, Amal, Alqubaishi, Fatmah, Ahmad, Maqsood, Al-Banyan, Ayman, Alotabi, Fahad E., Barakeh, Duna, AlZahrani, Malak, Al-Khalidi, Hisham, Ajlan, Abdulrazag, Ramkissoon, Lori A., Ramkissoon, Shakti H., Abedalthagafi, Malak
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988947/
https://www.ncbi.nlm.nih.gov/pubmed/31995621
http://dx.doi.org/10.1371/journal.pone.0228356
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author Mobark, Nahla A.
Alharbi, Musa
Alhabeeb, Lamees
AlMubarak, Latifa
Alaljelaify, Rasha
AlSaeed, Mariam
Almutairi, Amal
Alqubaishi, Fatmah
Ahmad, Maqsood
Al-Banyan, Ayman
Alotabi, Fahad E.
Barakeh, Duna
AlZahrani, Malak
Al-Khalidi, Hisham
Ajlan, Abdulrazag
Ramkissoon, Lori A.
Ramkissoon, Shakti H.
Abedalthagafi, Malak
author_facet Mobark, Nahla A.
Alharbi, Musa
Alhabeeb, Lamees
AlMubarak, Latifa
Alaljelaify, Rasha
AlSaeed, Mariam
Almutairi, Amal
Alqubaishi, Fatmah
Ahmad, Maqsood
Al-Banyan, Ayman
Alotabi, Fahad E.
Barakeh, Duna
AlZahrani, Malak
Al-Khalidi, Hisham
Ajlan, Abdulrazag
Ramkissoon, Lori A.
Ramkissoon, Shakti H.
Abedalthagafi, Malak
author_sort Mobark, Nahla A.
collection PubMed
description Pediatric Low Grade Gliomas (PLGGs) display heterogeneity regarding morphology, genomic drivers and clinical outcomes. The treatment modality dictates the outcome and optimizing patient management can be challenging. In this study, we profiled a targeted panel of cancer-related genes in 37 Saudi Arabian patients with pLGGs to identify genetic abnormalities that can inform prognostic and therapeutic decision-making. We detected genetic alterations (GAs) in 97% (36/37) of cases, averaging 2.51 single nucleotide variations (SNVs) and 0.91 gene fusions per patient. The KIAA1549-BRAF fusion was the most common alteration (21/37 patients) followed by AFAP1-NTRK2 (2/37) and TBLXR-PI3KCA (2/37) fusions that were observed at much lower frequencies. The most frequently mutated) genes were NOTCH1-3 (7/37), ATM (4/37), RAD51C (3/37), RNF43 (3/37), SLX4 (3/37) and NF1 (3/37). Interestingly, we identified a GOPC-ROS1 fusion in an 8-year-old patient whose tumor lacked BRAF alterations and histologically classified as low grade glioma. The patient underwent gross total resection (GTR). The patient is currently disease free. To our knowledge this is the first report of GOPC-ROS1 fusion in PLGG. Taken together, we reveal the genetic characteristics of pLGG patients can enhance diagnostics and therapeutic decisions. In addition, we identified a GOPC-ROS1 fusion that may be a biomarker for pLGG.
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spelling pubmed-69889472020-02-04 Clinical management and genomic profiling of pediatric low-grade gliomas in Saudi Arabia Mobark, Nahla A. Alharbi, Musa Alhabeeb, Lamees AlMubarak, Latifa Alaljelaify, Rasha AlSaeed, Mariam Almutairi, Amal Alqubaishi, Fatmah Ahmad, Maqsood Al-Banyan, Ayman Alotabi, Fahad E. Barakeh, Duna AlZahrani, Malak Al-Khalidi, Hisham Ajlan, Abdulrazag Ramkissoon, Lori A. Ramkissoon, Shakti H. Abedalthagafi, Malak PLoS One Research Article Pediatric Low Grade Gliomas (PLGGs) display heterogeneity regarding morphology, genomic drivers and clinical outcomes. The treatment modality dictates the outcome and optimizing patient management can be challenging. In this study, we profiled a targeted panel of cancer-related genes in 37 Saudi Arabian patients with pLGGs to identify genetic abnormalities that can inform prognostic and therapeutic decision-making. We detected genetic alterations (GAs) in 97% (36/37) of cases, averaging 2.51 single nucleotide variations (SNVs) and 0.91 gene fusions per patient. The KIAA1549-BRAF fusion was the most common alteration (21/37 patients) followed by AFAP1-NTRK2 (2/37) and TBLXR-PI3KCA (2/37) fusions that were observed at much lower frequencies. The most frequently mutated) genes were NOTCH1-3 (7/37), ATM (4/37), RAD51C (3/37), RNF43 (3/37), SLX4 (3/37) and NF1 (3/37). Interestingly, we identified a GOPC-ROS1 fusion in an 8-year-old patient whose tumor lacked BRAF alterations and histologically classified as low grade glioma. The patient underwent gross total resection (GTR). The patient is currently disease free. To our knowledge this is the first report of GOPC-ROS1 fusion in PLGG. Taken together, we reveal the genetic characteristics of pLGG patients can enhance diagnostics and therapeutic decisions. In addition, we identified a GOPC-ROS1 fusion that may be a biomarker for pLGG. Public Library of Science 2020-01-29 /pmc/articles/PMC6988947/ /pubmed/31995621 http://dx.doi.org/10.1371/journal.pone.0228356 Text en © 2020 Mobark et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Mobark, Nahla A.
Alharbi, Musa
Alhabeeb, Lamees
AlMubarak, Latifa
Alaljelaify, Rasha
AlSaeed, Mariam
Almutairi, Amal
Alqubaishi, Fatmah
Ahmad, Maqsood
Al-Banyan, Ayman
Alotabi, Fahad E.
Barakeh, Duna
AlZahrani, Malak
Al-Khalidi, Hisham
Ajlan, Abdulrazag
Ramkissoon, Lori A.
Ramkissoon, Shakti H.
Abedalthagafi, Malak
Clinical management and genomic profiling of pediatric low-grade gliomas in Saudi Arabia
title Clinical management and genomic profiling of pediatric low-grade gliomas in Saudi Arabia
title_full Clinical management and genomic profiling of pediatric low-grade gliomas in Saudi Arabia
title_fullStr Clinical management and genomic profiling of pediatric low-grade gliomas in Saudi Arabia
title_full_unstemmed Clinical management and genomic profiling of pediatric low-grade gliomas in Saudi Arabia
title_short Clinical management and genomic profiling of pediatric low-grade gliomas in Saudi Arabia
title_sort clinical management and genomic profiling of pediatric low-grade gliomas in saudi arabia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988947/
https://www.ncbi.nlm.nih.gov/pubmed/31995621
http://dx.doi.org/10.1371/journal.pone.0228356
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