Table 2.
A summary of recommended biomarkers for testing.
| Adjuvant therapy (evidence level) | |||||||||
| Biomarkers | Function | Tumor location | Clinical significance (evidence level) | Diagnosis (evidence level) | Radiation therapy | Systemic therapy | Follow-up (evidence level) | Test method | Recommendation grade |
| Copy number alterations | |||||||||
| 22q | A critical role in meningiomagenesis by dysregulating oncogene and tumor suppressor activity | Convexity and spine | 22q loss is significantly associated with worse clinical outcome (evidence 2B) | Unknown | Unknown | Sensitive to sunitinib (evidence 3) | Annually within 5 years (evidence 3) | Karyotyping, FISH, Array-CGH, NGS | Grade I |
| 1p | Unknown | Unknown | 1p loss is associated with worse clinical outcome (evidence 2A). 1p/14q loss increases the risk of tumor recurrence (evidence 2A) | Unknown | Unknown | Sensitive to sunitinib (evidence 3) | Every 6 months within 5 years (evidence 3) | Karyotyping, FISH, Array-CGH, NGS | Grade I |
| 14q | Unknown | Unknown | 1p/14q loss increases the risk of tumor recurrence (evidence 2A) | Unknown | Unknown | Unknown | Every 6 months within 5 years (evidence 3) | Karyotyping, FISH, Array-CGH, NGS | Grade I |
| 18q | Unknown | Unknown | 18q loss increases the risk of tumor short-term recurrence (evidence 2B) | Unknown | Unknown | Unknown | Annually within 5 years (evidence 3) | Karyotyping, FISH, Array-CGH, NGS | Grade III |
| Gene mutation signatures | |||||||||
| NF2 | NF2 produces merlin that functions as a tumor suppressor by inhibiting cell growth | Convexity and spine | NF2 mutation is associated with worse clinical outcome, increases the risk of tumor recurrence (evidence 2A) | Unknown | Unknown | Unknown | Annually within 5 years (evidence 3) | NGS, Sanger sequence, MLPA, FISH, IHC | Grade I |
| TERT promoter | TERTp regulates TERT gene expression and maintains normal cell mitosis | Unknown | TERTp mutation is associated with worse clinical outcome, and increases the risk of tumor recurrence (evidence 1A) | Histological criteria of WHO grade 3 (evidence 3) | TERTp alteration is associated with radiation sensitivity in de novo high-grade meningiomas (evidence 2B) | Unknown | Every 3–6 months indefinitely (evidence 3) | NGS, Sanger sequence | Grade I |
| CDKN2A/B | CDKN2A/B regulates cell cycle and inhibits tumor cell proliferation | Unknown | CDKN2A/B mutation is associated with worse clinical outcome, and increases the risk of tumor recurrence (evidence 2A) | Histological criteria of WHO grade 3 (evidence 3) | Unknown | Unknown | Every 6 months within 5 years (evidence 3) | NGS, Sanger sequence | Grade I |
| AKT1, PIK3CA | PI3K pathway serves to disconnect the control of cell growth, survival and metabolism from exogenous growth stimuli | Middle fossa skull base | AKT1 and PIK3CA mutation increases the risk of tumor recurrence (evidence 2A) | Unknown | Unknown | Everolimus-octreotide (evidence 2A); everolimus-bevacizumab (evidence 2A) | Every 6 months within 5 years (evidence 3) | AKT1: NGS, RT-PCR; PIK3CA: NGS, Sanger sequence, RT-PCR | Grade I |
| SMO, SUFU | Driver genes in Hedgehog pathway | Middle fossa skull base | SMO and SUFU mutation increases the risk of tumor recurrence (evidence 2A) | Unknown | Unknown | Unknown | Annually within 5 years (evidence 3) | SMO: NGS, Sanger sequence; SUFU: NGS, IHC | Grade I |
| TRAF7 | Transduction molecules in TNFR mediated signaling pathway | Middle fossa skull base | TRAF mutation increases the risk of tumor short-term recurrence (evidence 2A) | Histological criteria of secretory subtype (evidence 3) | Unknown | Unknown | – | NGS, Sanger sequence | Grade I |
| KLF4 | Zinc finger protein transcription factor, which involves in the regulation of cell proliferation, differentiation and embryonic development | Non-midline anterior and central skull base | KLF4 mutation is associated with better 5-year progression-free survival and peritumoral brain edema (evidence 2A) | Histological criteria of secretory subtype (evidence 3) | Unknown | Unknown | – | NGS, Sanger sequence | Grade I |
| SMARCE1 | Chromatin remodeling complex SWI/SNF involves in encoding part of ATP | Spine | Common mutation in clear cell subtype (evidence 2A) | Reference for diagnosis of secretory subtype (evidence 3) | Unknown | Unknown | – | NGS, IHC | Grade I |
| BAP1 | A tumor suppressor gene that encodes a deubiquitylating enzyme, and inhibits tumor growth by binding to the ring finger domain of BRCA1 | Unknown | BAP1 mutation is associated with worse clinical outcome, and increases the risk of tumor recurrence (evidence 2A) | Reference for diagnosis of rhabdoid subtype (evidence 3) | Unknown | Unknown | Every 6 months within 5 years (evidence 3) | NGS, IHC | Grade I |
| DMD | DMD locates at Xp21.1-p21.3, encoding dystrophin | Unknown | DMD mutation is associated with worse clinical outcome, and increases the risk of tumor recurrence (evidence 2B) | Unknown | Unknown | Unknown | Annually within 5 years (evidence 3) | NGS, IHC | Grade I |
| PBRM1 | A tumor suppressor gene encoding the BAF180 subunit of the SWI/SNF complex, and involving in the regulation of tumor cell proliferation and migration | Unknown | Common mutation in papillary subtype (evidence 2B) | Unknown | Unknown | Unknown | – | NGS | Grade III |
| POLR2A | The protein that mediates transcription of all protein-coding genes in eukaryotes | Anterior skull base, especially tuberculum sellae | POLR2A mutation is associated with better clinical outcome (evidence 2B) | Unknown | Unknown | Unknown | – | NGS, Sanger sequence | Grade III |
| Epigenomic alterations | |||||||||
| H3K27me3 | A chromatin modification that is tightly linked to gene repression and plays an essential role in the development and progression of intracranial tumors | Unknown | H3K27me3 loss increases the risk of tumor short-term recurrence (evidence 2A) | Unknown | Unknown | Unknown | Every 6 months within 5 years (evidence 3) | IHC | Grade I |
| TIMP3 methylation | TIMP3 methylation causes a down-regulation in transcription product and then loss of tumor suppressor activity | Unknown | TIMP3 methylation increases the risk of tumor short-term recurrence (evidence 2B) | Unknown | Unknown | Unknown | Every 6 months within 5 years (evidence 3) | Pyrosequencing | Grade II |
| TP73 promoter methylation | TP73 promoter methylation regulates downstream transcripts and inhibits tumor growth | Unknown | TP73 promoter methylation increases the risk of tumor short-term recurrence (evidence 2B) | Unknown | Unknown | Unknown | Every 6 months within 5 years (evidence 3) | Pyrosequencing | Grade II |
| Hormone receptors | |||||||||
| ER | ER participates in regulation of multiple hormones, inhibits cell proliferation and promotes cell apoptosis | Unknown | High expression of ER is associated with worse clinical outcome (evidence 2B) | Unknown | Unknown | Unknown | – | IHC | Grade III |
| PR | PR participates in regulation of multiple hormones, inhibits cell proliferation and promotes cell apoptosis | Unknown | High expression of PR is associated with worse clinical outcome (evidence 2B) | Unknown | Unknown | Unknown | – | IHC | Grade III |
| SSTR2 | SSTR2 participates in regulation of multiple hormones, inhibits cell proliferation and promotes cell apoptosis | Unknown | SSTR2 alterations increase the risk of tumor recurrence (evidence 2B) | Octreotide-scanning (evidence 2B) | Unknown | Everolimus-octreotide (evidence 2B) | – | IHC | Grade I |
| Tyrosine kinases receptors | |||||||||
| VEGFR | VEGFR involves in regulation of lymphatic endothelial cells and vascular endothelial cells, and promotes the formation of lymphatic vessels and blood vessels | Unknown | Expressien of VEGFR is associated with higher WHO grade and shorter progression-free survival (evidence 2B) | Unknown | Unknown | Bevacizumab (evidence 2A) | – | IHC | Grade II |
AKT1: Protein kinase B; Array-CGH: Array-comparative genomic hybridization; ATP: Adenosine triphosphate; BAF: BRM-associated factor; BAP1: BRCA1 associated protein 1; BRCA1: Breast cancer 1; CDKN2A/B: Cyclin-dependent kinase inhibitor 2A/B; DMD: Duchenne muscular dystrophy; ER: Estrogen receptor; FISH: Fluorescence in situ hybridization; H3K27me3: Trimethylation of lysine 27 on histone 3; IHC: Immunohistochemistry; KLF4: Krüppel-like factor 4; MLPA: Multiple ligation-dependent probe amplification; NF2: Neurofibromin 2; NGS: Next generation sequencing; PBRM1: Polybromo-1; PI3K: Phosphosphatidylinositol-3-kinase; PIK3CA: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha isoform; POLR2A: RNA polymerase II; PR: Progesterone Receptor; RT-PCR: Reverse transcription-polymerase chain reaction; SMARCE1: SWI/SNF Related, matrix associated, actin dependent regulator of chromatin, subfamily E, member 1; SMO: Smoothened; SSTR2: Somatostatin receptor 2; SUFU: Suppressor of fused homolog; SWI/SNF: Switching defective/sucrose non-fermenting; TERT: Telomerase reverse tranase; TERTp: Telomerase reverse transcriptase promoter; TIMP3: Tissue inhibitor of matrix metalloproteinase 3; TNFR: Tumor necrosis factor receptor; TP73: Tumor protein p73; TRAF7: Tumor necrosis factor receptor associated factor 7; VEGFR: Vascular endothelial growth factor receptor; WHO: World Health Organization; -: Not available.