A Rapid Robust Method for Subgrouping Non-NF2 Meningiomas According to Genotype and Detection of Lower Levels of M2 Macrophages in AKT1 E17K Mutated Tumours

被引:18
作者
Adams, Claire L. [1 ]
Ercolano, Emanuela [1 ]
Ferluga, Sara [1 ]
Sofela, Agbolahan [1 ,2 ]
Dave, Foram [1 ]
Negroni, Caterina [1 ]
Kurian, Kathreena M. [3 ,4 ]
Hilton, David A. [5 ]
Hanemann, C. Oliver [1 ]
机构
[1] Univ Plymouth, Fac Hlth Med Dent & Human Sci, Inst Translat & Stratified Med, John Bull Bldg,Plymouth Sci Pk,Res Way, Plymouth PL6 8BU, Devon, England
[2] Univ Hosp Plymouth NHS Trust, Dept Neurosurg, Derriford Rd, Plymouth PL6 8DH, Devon, England
[3] Univ Bristol, Inst Clin Neurosci, Bristol BS8 1QU, Avon, England
[4] North Bristol Trust, Southmead Hosp, Bristol BS8 1QU, Avon, England
[5] Univ Hosp Plymouth NHS Trust, Cellular & Anat Pathol, Derriford Rd, Plymouth PL6 8DH, Devon, England
基金
英国医学研究理事会;
关键词
meningioma; M2; macrophage; genotype; AKT1; E17K; NF2; non-NF2; MUTATIONS; EXPRESSION; AKT1; ACTIVATION; SYSTEM; CLASSIFICATION; FREQUENT; CELLS; GENE; TIME;
D O I
10.3390/ijms21041273
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The majority of meningiomas are grade I, but some grade I tumours are clinically more aggressive. Recent advances in the genetic study of meningiomas has allowed investigation into the influence of genetics on the tumour microenvironment, which is important for tumorigenesis. We have established that the endpoint genotyping method Kompetitive Allele Specific PCR (KASP (TM)) is a fast, reliable method for the screening of meningioma samples into different non-NF2 mutational groups using a standard real-time PCR instrument. This genotyping method and four-colour flow cytometry has enabled us to assess the variability in the largest immune cell infiltrate population, M2 macrophages (CD45(+)HLA-DR(+)CD14(+)CD163(+)) in 42 meningioma samples, and to suggest that underlying genetics is relevant. Further immunohistochemistry analysis comparing AKT1 E17K mutants to WHO grade I NF2-negative samples showed significantly lower levels of CD163-positive activated M2 macrophages in meningiomas with mutated AKT1 E17K, signifying a more immunosuppressive tumour microenvironment in NF2 meningiomas. Our data suggested that underlying tumour genetics play a part in the development of the immune composition of the tumour microenvironment. Stratifying meningiomas by mutational status and correlating this with their cellular composition will aid in the development of new immunotherapies for patients.
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