Marei Hany E, Althani Asmaa, Afifi Nahla, Hasan Anwarul, Caceci Thomas, Felsani Armando, Tringali Giuseppe, Cifola Ingrid, Pozzoli Giacomo, Cenciarelli Carlo
Department of Cytology and Histology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, 35116, Egypt.
Biomedical Research Center, Qatar University, Doha, Qatar.
Cancer Cell Int. 2022 Jan 7;22(1):9. doi: 10.1186/s12935-021-02419-4.
Glioblastoma 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.
In 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.
By 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.
We 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.
多形性胶质母细胞瘤（GBM）是一种异质性中枢神经系统肿瘤，会导致严重的发病率和死亡率。GBM预后不良的一个原因是存在癌症干细胞（CSC），其赋予对标准化学疗法和放射治疗方式的抗性。从同一患者中分离出两种与GBM相关的CSC：肿瘤核心（c-CSC）和肿瘤周围组织来源的癌症干细胞（p-CSC）。我们的实验聚焦于胶质母细胞瘤-IDH野生型，并且在组蛋白、BRAF或其他基因中不存在疾病定义性改变。
在本研究中，研究了来自四名GBM患者的c-CSC与p-CSC之间遗传变异的潜在差异，目的是（1）比较所有c-CSC或p-CSC之间的外显子组序列以鉴定常见变异；（2）鉴定影响已知参与癌症起源和发展的基因功能的变异。
通过比较分析，我们在所有GBM的c-CSC和p-CSC中鉴定出常见基因单核苷酸变异（SNV），一个潜在有害变异是MLLT1基因中Gln461fs处的移码缺失，仅在具有不同等位基因频率的p-CSC样本中出现。
我们在MLLT1基因中发现了一个潜在有害的Gln461fs移码缺失。需要进一步研究以确认患者组织样本中所鉴定突变是否存在，以及基于基因组功能实验确定MLLT1基因中的移码突变对GBM生物学和治疗反应的意义。
