Integrated molecular and clinical analysis of 1,000 pediatric low-grade gliomas Journal Article
| Authors: | Ryall, S.; Zapotocky, M.; Fukuoka, K.; Nobre, L.; Guerreiro Stucklin, A.; Bennett, J.; Siddaway, R.; Li, C.; Pajovic, S.; Arnoldo, A.; Kowalski, P. E.; Johnson, M.; Sheth, J.; Lassaletta, A.; Tatevossian, R. G.; Orisme, W.; Qaddoumi, I.; Surrey, L. F.; Li, M. M.; Waanders, A. J.; Gilheeney, S.; Rosenblum, M.; Bale, T.; Tsang, D. S.; Laperriere, N.; Kulkarni, A.; Ibrahim, G. M.; Drake, J.; Dirks, P.; Taylor, M. D.; Rutka, J. T.; Laughlin, S.; Shroff, M.; Shago, M.; Hazrati, L. N.; D'Arcy, C.; Ramaswamy, V.; Bartels, U.; Huang, A.; Bouffet, E.; Karajannis, M. A.; Santi, M.; Ellison, D. W.; Tabori, U.; Hawkins, C. |
| Article Title: | Integrated molecular and clinical analysis of 1,000 pediatric low-grade gliomas |
| Abstract: | Pediatric low-grade gliomas (pLGG) are frequently driven by genetic alterations in the RAS-mitogen-activated protein kinase (RAS/MAPK) pathway yet show unexplained variability in their clinical outcome. To address this, we characterized a cohort of >1,000 clinically annotated pLGG. Eighty-four percent of cases harbored a driver alteration, while those without an identified alteration also often exhibited upregulation of the RAS/MAPK pathway. pLGG could be broadly classified based on their alteration type. Rearrangement-driven tumors were diagnosed at a younger age, enriched for WHO grade I histology, infrequently progressed, and rarely resulted in death as compared with SNV-driven tumors. Further sub-classification of clinical-molecular correlates stratified pLGG into risk categories. These data highlight the biological and clinical differences between pLGG subtypes and opens avenues for future treatment refinement. © 2020 Elsevier Inc. Ryall et al. perform a comprehensive analysis of the molecular underpinnings and clinical correlates of 1000 pediatric low-grade gliomas. They uncover unique clinical features based on the type of molecular alteration identified and provide a risk based stratification to help infer treatment decisions. © 2020 Elsevier Inc. |
| Keywords: | signal transduction; mitogen activated protein kinase; adolescent; adult; child; controlled study; human tissue; unclassified drug; gene mutation; major clinical study; single nucleotide polymorphism; histopathology; comparative study; molecular genetics; brain tumor; glioma; cancer grading; cohort analysis; genetic variability; protein tyrosine kinase; tumor marker; childhood cancer; pediatric; age; cancer genetics; correlation coefficient; death; gene rearrangement; infant; histone h3; newborn; gene fusion; risk stratification; world health organization; upregulation; cyclin dependent kinase inhibitor 2a; cancer classification; k ras protein; b raf kinase; neurooncology; fibroblast growth factor receptor 1; fibroblast growth factor receptor 2; scatter factor receptor; brain derived neurotrophic factor receptor; anaplastic lymphoma kinase; molecular pathology; platelet derived growth factor b; isocitrate dehydrogenase 1; peptides and proteins; low-grade glioma; molecular diagnostics; protein myb; human; male; female; priority journal; article; receptor tyrosine kinase like orphan receptor; mybl1 protein; pediatric patient; molecular fingerprinting; ras/mapk pathway; ccdc88a protein; gopc protein; mid1 protein; ppp1cb protein; ros1 protein; tacc1 protein |
| Journal Title: | Cancer Cell |
| Volume: | 37 |
| Issue: | 4 |
| ISSN: | 1535-6108 |
| Publisher: | Cell Press |
| Date Published: | 2020-04-13 |
| Start Page: | 569 |
| End Page: | 583.e5 |
| Language: | English |
| DOI: | 10.1016/j.ccell.2020.03.011 |
| PUBMED: | 32289278 |
| PROVIDER: | scopus |
| PMCID: | PMC7169997 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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