Comprehensive mutation analysis of the ras/raf/mek/erk pathway in paediatric leukaemia and significant inferences

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dc.contributor.authorAkin-Bali, Dilara Fatma
dc.contributor.authorAktas, Sedef Hande
dc.contributor.authorOzcan, Alper
dc.contributor.authorYilmaz, Ebru
dc.contributor.authorAydin, Firdevs
dc.contributor.authorGök, Veysel
dc.contributor.authorÜnal, Ekrem
dc.date.accessioned2024-11-07T10:39:44Z
dc.date.available2024-11-07T10:39:44Z
dc.date.issued2021
dc.departmentNiğde Ömer Halisdemir Üniversitesi
dc.description.abstractObjectives: Leukaemia is the most common cancer among paediatric population accounting for about 30% of paediatric cancer. As it's known, germ line mutations increase the risk of development of haematopoietic malignancy in childhood and deregulation of the Rat Sarcoma Viral Proto-Oncogene/ Raf-1 Proto-Oncogene/Mitogen-Activated Protein Kinases/Extracellular Regulated Kinases (RAS/RAF/ MEK/ERK) pathway is often caused by somatic mutations in the genes coding proteins of KRAS, NRAS, FLT3, PTPN11 and BRAF. However, mutations in this pathway in paediatric Acute Lymphoblastic Leukaemia (ALL) have not been thoroughly investigated, yet. Methods: Specific exons of 7 significant genes which were frequently mutated in the RAS/RAF/MEK/ERK pathway were determined inclusively by DNA sequence analysis in 27 children with leukaemia. PolyPhen-2 and SNAP tools were used to verify and estimate the determined changes. Also, evolutionary conservation analysis was performed. Results: Seven changes out of 22 changes were identified for the first time in this study. ERK2 p.P319S (18.5%) mutation and KRAS splice site mutation (3.7%) were predicted to be pathogenic. ERK2 p.P319S mutations was found to be pathogenic and at the critical point on the aminoacid which is evalutionary conserved. Although the frequency of mutations in ERK2 is very low in cancers (0.88%), the frequency of ERK2 p.P319S missense change was detected in our study at a significant rate such as 18.5%. Conclusion: There is limited knowledge about ERK inhibitors in leukaemia. The low frequency of ERK gene compared to KRAS and NRAS genes does not make ERK mutations less important. Our findings indicate the importance of this pathway mutations in paediatric ALL and associated with high risk leukaemia group characteristics. Hence, it can be evaluated as a signalisation pathway to target pharmacologically. © 2021, Medcom Limited. All rights reserved.
dc.description.sponsorshipScientific Research Projects of Nigde Omer Halisdemir University, (SSB 2018/11-BAGEP)
dc.identifier.endpage87
dc.identifier.issn1013-9923
dc.identifier.issue2
dc.identifier.scopus2-s2.0-85105382172
dc.identifier.scopusqualityQ4
dc.identifier.startpage75
dc.identifier.urihttps://hdl.handle.net/11480/11147
dc.identifier.volume26
dc.indekslendigikaynakScopus
dc.language.isoen
dc.publisherMedcom Limited
dc.relation.ispartofHong Kong Journal of Paediatrics
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_20241106
dc.subjectALL
dc.subjectMutation
dc.subjectPaediatric leukaemia
dc.subjectRAS/RAF/MEK/ERK pathway
dc.titleComprehensive mutation analysis of the ras/raf/mek/erk pathway in paediatric leukaemia and significant inferences
dc.typeArticle

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