Exome sequencing of glioblastoma-derived cancer stem cells reveals rare clinically relevant frameshift deletion in MLLT1 gene

Cancer Cell International

Asmaa Althani¹  Thomas Caceci²  Hany E. Marei³  Anwarul Hasan⁴  Armando Felsani⁵  Ingrid Cifola⁶  Giuseppe Tringali⁷  Carlo Cenciarelli⁸  Giacomo Pozzoli⁹  Nahla Afifi^1,10 

[1] Biomedical Research Center, Qatar University, Doha, Qatar;Biomedical Sciences, Virginia Maryland College of Veterinary Medicine, Blacksburg, VA, USA;Department of Cytology and Histology, Faculty of Veterinary Medicine, Mansoura University, 35116, Mansoura, Egypt;Department of Mechanical and Industrial Engineering, College of Engineering, Qatar University, Doha, Qatar;Genomnia S.R.L, Via Ludovico Ariosto, 20091, Bresso, MI, USA;Institute for Biomedical Technologies (ITB), National Research Council (CNR), Milan, Italy;Institute of Pharmacology, Catholic University School of Medicine, Rome, Italy;Institute of Translational Pharmacology (IFT), National Research Council (CNR), Via Fosso del Cavaliere, 100, 00133, Rome, Italy;Pharmacology Unit, Fondazione Policlinico A. Gemelli, IRCCS, Rome, Italy;Institute of Translational Pharmacology (IFT), National Research Council (CNR), Via Fosso del Cavaliere, 100, 00133, Rome, Italy;Qatar Biobank, Doha, Qatar;

关键词: GBM;    Exome;    Sequencing;    Cancer stem cells;    Genetic variants;   

DOI  :  10.1186/s12935-021-02419-4

来源: Springer

【 摘 要 】

BackgroundGlioblastoma multiforme (GBM) is a heterogeneous CNS neoplasm which causes significant morbidity and mortality. One reason for the poor prognostic outcome of GBM is attributed to the presence of cancer stem cells (CSC) which confer resistance against standard chemo- and radiotherapeutics modalities. Two types of GBM-associated CSC were isolated from the same patient: tumor core- (c-CSC) and peritumor tissue-derived cancer stem cells (p-CSC). Our experiments are focused on glioblastoma–IDH-wild type, and no disease-defining alterations were present in histone, BRAF or other genes.MethodsIn the present study, potential differences in genetic variants between c-CSC versus p-CSC derived from four GBM patients were investigated with the aims of (1) comparing the exome sequences between all the c-CSC or p-CSC to identify the common variants; (2) identifying the variants affecting the function of genes known to be involved in cancer origin and development.ResultsBy comparative analyses, we identified common gene single nucleotide variants (SNV) in all GBM c-CSC and p-CSC, a potentially deleterious variant was a frameshift deletion at Gln461fs in the MLLT1 gene, that was encountered only in p-CSC samples with different allelic frequency.ConclusionsWe discovered a potentially harmful frameshift deletion at Gln461fs in the MLLT1 gene. Further investigation is required to confirm the presence of the identified mutations in patient tissue samples, as well as the significance of the frameshift mutation in the MLLT1 gene on GBM biology and response to therapy based on genomic functional experiments.

【 授权许可】

CC BY