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Article: Pediatric low-grade gliomas can be molecularly stratified for risk

TitlePediatric low-grade gliomas can be molecularly stratified for risk
Authors
KeywordsATRX
BRAF
CDKN2A
H3F3A
Molecular risk stratification
Pediatric low-grade gliomas
Issue Date2018
Citation
Acta Neuropathologica, 2018, v. 136, n. 4, p. 641-655 How to Cite?
AbstractPediatric low-grade gliomas (PLGGs) consist of a number of entities with overlapping histological features. PLGGs have much better prognosis than the adult counterparts, but a significant proportion of PLGGs suffers from tumor progression and recurrence. It has been shown that pediatric and adult low-grade gliomas are molecularly distinct. Yet the clinical significance of some of newer biomarkers discovered by genomic studies has not been fully investigated. In this study, we evaluated in a large cohort of 289 PLGGs a list of biomarkers and examined their clinical relevance. TERT promoter (TERTp), H3F3A and BRAF V600E mutations were detected by direct sequencing. ATRX nuclear loss was examined by immunohistochemistry. CDKN2A deletion, KIAA1549-BRAF fusion, and MYB amplification were determined by fluorescence in situ hybridization (FISH). TERTp, H3F3A, and BRAF V600E mutations were identified in 2.5, 6.4, and 7.4% of PLGGs, respectively. ATRX loss was found in 4.9% of PLGGs. CDKN2A deletion, KIAA1549-BRAF fusion and MYB amplification were detected in 8.8, 32.0 and 10.6% of PLGGs, respectively. Survival analysis revealed that TERTp mutation, H3F3A mutation, and ATRX loss were significantly associated with poor PFS (p < 0.0001, p < 0.0001, and p = 0.0002) and OS (p < 0.0001, p < 0.0001, and p < 0.0001). BRAF V600E was associated with shorter PFS (p = 0.011) and OS (p = 0.032) in a subset of PLGGs. KIAA1549-BRAF fusion was a good prognostic marker for longer PFS (p = 0.0017) and OS (p = 0.0029). MYB amplification was also a favorable marker for a longer PFS (p = 0.040). Importantly, we showed that these molecular biomarkers can be used to stratify PLGGs into low- (KIAA1549-BRAF fusion or MYB amplification), intermediate-I (BRAF V600E and/or CDKN2A deletion), intermediate-II (no biomarker), and high-risk (TERTp or H3F3A mutation or ATRX loss) groups with distinct PFS (p < 0.0001) and OS (p < 0.0001). This scheme should aid in clinical decision-making.
Persistent Identifierhttp://hdl.handle.net/10722/325390
ISSN
2023 Impact Factor: 9.3
2023 SCImago Journal Rankings: 4.720
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorYang, Rui Ryan-
dc.contributor.authorAibaidula, Abudumijiti-
dc.contributor.authorWang, Wei wei-
dc.contributor.authorChan, Aden Ka Yin-
dc.contributor.authorShi, Zhi feng-
dc.contributor.authorZhang, Zhen yu-
dc.contributor.authorChan, Danny Tat Ming-
dc.contributor.authorPoon, Wai Sang-
dc.contributor.authorLiu, Xian zhi-
dc.contributor.authorLi, Wen cai-
dc.contributor.authorZhang, Rui qi-
dc.contributor.authorLi, Yan Xi-
dc.contributor.authorChung, Nellie Yuk Fei-
dc.contributor.authorChen, Hong-
dc.contributor.authorWu, Jingsong-
dc.contributor.authorZhou, Liangfu-
dc.contributor.authorLi, Kay Ka Wai-
dc.contributor.authorNg, Ho Keung-
dc.date.accessioned2023-02-27T07:32:28Z-
dc.date.available2023-02-27T07:32:28Z-
dc.date.issued2018-
dc.identifier.citationActa Neuropathologica, 2018, v. 136, n. 4, p. 641-655-
dc.identifier.issn0001-6322-
dc.identifier.urihttp://hdl.handle.net/10722/325390-
dc.description.abstractPediatric low-grade gliomas (PLGGs) consist of a number of entities with overlapping histological features. PLGGs have much better prognosis than the adult counterparts, but a significant proportion of PLGGs suffers from tumor progression and recurrence. It has been shown that pediatric and adult low-grade gliomas are molecularly distinct. Yet the clinical significance of some of newer biomarkers discovered by genomic studies has not been fully investigated. In this study, we evaluated in a large cohort of 289 PLGGs a list of biomarkers and examined their clinical relevance. TERT promoter (TERTp), H3F3A and BRAF V600E mutations were detected by direct sequencing. ATRX nuclear loss was examined by immunohistochemistry. CDKN2A deletion, KIAA1549-BRAF fusion, and MYB amplification were determined by fluorescence in situ hybridization (FISH). TERTp, H3F3A, and BRAF V600E mutations were identified in 2.5, 6.4, and 7.4% of PLGGs, respectively. ATRX loss was found in 4.9% of PLGGs. CDKN2A deletion, KIAA1549-BRAF fusion and MYB amplification were detected in 8.8, 32.0 and 10.6% of PLGGs, respectively. Survival analysis revealed that TERTp mutation, H3F3A mutation, and ATRX loss were significantly associated with poor PFS (p < 0.0001, p < 0.0001, and p = 0.0002) and OS (p < 0.0001, p < 0.0001, and p < 0.0001). BRAF V600E was associated with shorter PFS (p = 0.011) and OS (p = 0.032) in a subset of PLGGs. KIAA1549-BRAF fusion was a good prognostic marker for longer PFS (p = 0.0017) and OS (p = 0.0029). MYB amplification was also a favorable marker for a longer PFS (p = 0.040). Importantly, we showed that these molecular biomarkers can be used to stratify PLGGs into low- (KIAA1549-BRAF fusion or MYB amplification), intermediate-I (BRAF V600E and/or CDKN2A deletion), intermediate-II (no biomarker), and high-risk (TERTp or H3F3A mutation or ATRX loss) groups with distinct PFS (p < 0.0001) and OS (p < 0.0001). This scheme should aid in clinical decision-making.-
dc.languageeng-
dc.relation.ispartofActa Neuropathologica-
dc.subjectATRX-
dc.subjectBRAF-
dc.subjectCDKN2A-
dc.subjectH3F3A-
dc.subjectMolecular risk stratification-
dc.subjectPediatric low-grade gliomas-
dc.titlePediatric low-grade gliomas can be molecularly stratified for risk-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1007/s00401-018-1874-3-
dc.identifier.pmid29948154-
dc.identifier.scopuseid_2-s2.0-85048564495-
dc.identifier.volume136-
dc.identifier.issue4-
dc.identifier.spage641-
dc.identifier.epage655-
dc.identifier.eissn1432-0533-
dc.identifier.isiWOS:000443549100009-

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