Table 3.
Summary of Biomarkers Identified for Primary Brain and Other CNS Tumors and Collection Status in Central Cancer Registries
| Histology | Gene or Marker | Outcome | Collected by US Cancer Registry System |
|---|---|---|---|
| Glioma (especially oligodendroglial tumors)a-e | Large deletions (missing parts of the chromosome) in the short arm of chromosome 1 (1p) and the long arm of chromosome 19 (19q) | Improved response to chemotherapy and radiation, and increased survival | Yes Site-specific factor (SSF) 5 (2011–2017), SSF 6 (2011–2017) Site-Specific Data Items (SSDI): Chromosome 19q Status (2018+), SSDI: Chromosome 1p Status (2018+) |
| Glioma (especially low grade astrocytomas and oligodendroglial tumors)d-f | Protein-truncating mutation in isocitrate dehydrogenase 1 (IDH1) or in isocitrate dehydrogenase 2 (IDH2) | Increased survival time | Yes SSDI: Brain Molecular Markers (2018+) |
| Glioma (especially IDH mutated glioma)d,g,h | Loss of function mutation in alpha thalassemia/mental retardation syndrome X-linked (ATRX) | Increased survival time | No |
| Glioblastomae,i–m | Methylation of the promoter of O-6-methylguanine-DNA methyltransferase (MGMT) | Limits ability of the tumor cells to repair DNA damage caused by chemotherapy and radiation; results in increased survival time | Yes SSF 4 (2011–2017), SSDI: MGMT (2018+) |
| Glioma-CpG island methylator phenotype (G-CIMP), Genome-wide DNA methylation | Significantly increased survival time | No | |
| Amplification of epidermal growth factor receptor (EGFR) | Activates the RTK/RAS/PI3K pathway, leading to increased proliferation. Associated with poorer survival. | No | |
| Glioma (oligodendroglial tumors and IDH wild type glioblastoma)e,n,o | Mutation of promotor of Telomerase reverse transcriptase (TERT) | Facilitates increased telomere lengthening, and decreases survival in IDH wild type glioma | No |
| Glioma (particularly pediatric lower grade gliomas)p | Mutation or fusion of B-Raf (BRAF) | Activates the RAS/MAPK pathway. Fusion leads to improved survival. | No |
| Medulloblastomaq–u | WNT-activated | Low prevalence of metastatic disease Highest five-year survival |
Yes, Began in collection year 2018 (January 1), SSDI: Brain Molecular Markers (2018+) |
| SHH-activated and TP53-mutant | Occur primary in older children, very poor prognosis | Yes, Began in collection year 2018 (January 1), SSDI: Brain Molecular Markers (2018+) | |
| SHH-activated and TP53-wildtype | Most common in adolescents and young children, good prognosis | Yes, Began in collection year 2018 (January 1), SSDI: Brain Molecular Markers (2018+) | |
| non-WNT/non-SHH, Group 3 subtype (also known as Group C) | Increased prevalence of metastatic disease, Poorest five-year survival | ||
| non-WNT/non-SHH, Group 4 subtype (also known as Group D) | Increased prevalence of metastatic disease, Moderate five-year survival | ||
| Embryonal tumorv,w | C19MC amplification and presence of multilayered rosettes | Highly aggressive, with average survival of 12 months after diagnosis | Yes, Began in collection year 2018 (January 1), SSDI: Brain Molecular Markers (2018+) |
For more information please see:
aCairncross JG, et al. Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J Natl Cancer Inst. 1998; 90(19):1473–1479.
bVogelbaum MA, et al. Phase II trial of pre-irradiation and concurrent temozolomide in patients with newly diagnosed anaplastic oligodendrogliomas and mixed anaplastic oligoastrocytomas: long term results of RTOG BR0131. Journal of neuro-oncology. 2015; 124(3):413–420.
cvan den Bent MJ, et al. Adjuvant procarbazine, lomustine, and vincristine chemotherapy in newly diagnosed anaplastic oligodendroglioma: long-term follow-up of EORTC brain tumor group study 26951. J. Clin. Oncol. 2013; 31(3):344–350.
dThe Cancer Genome Atlas Research Network, et al. Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas. N. Engl. J. Med. 2015; 372(26):2481–2498.
eCeccarelli M, et al. Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma. Cell. 2016; 164(3):550–563.
fYan H, et al. IDH1 and IDH2 mutations in gliomas. N. Engl. J. Med. 2009; 360(8):765–773.
gJiao Y, et al. Frequent ATRX, CIC, FUBP1 and IDH1 mutations refine the classification of malignant gliomas. Oncotarget. 2012; 3(7):709–722.
hWiestler B, et al. ATRX loss refines the classification of anaplastic gliomas and identifies a subgroup of IDH mutant astrocytic tumors with better prognosis. Acta Neuropathol. 2013; 126(3):443–451.
iHegi ME, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N. Engl. J. Med. 2005; 352(10):997–1003.
jStupp R, et al. Chemoradiotherapy in malignant glioma: standard of care and future directions. J. Clin. Oncol. 2007; 25(26):4127–4136.
kHegi ME, et al. Correlation of O6-methylguanine methyltransferase (MGMT) promoter methylation with clinical outcomes in glioblastoma and clinical strategies to modulate MGMT activity. J. Clin. Oncol. 2008; 26(25):4189–4199.
lNoushmehr H, et al. Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma. Cancer Cell. 2010; 17(5):510–522.
mMaire CL, Ligon KL. Molecular pathologic diagnosis of epidermal growth factor receptor. Neuro Oncol. 2014; 16 Suppl 8:viii1-6.
nArita H, et al. Upregulating mutations in the TERT promoter commonly occur in adult malignant gliomas and are strongly associated with total 1p19q loss. Acta Neuropathol. 2013; 126(2):267–276.
oEckel-Passow JE, et al. Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors. N. Engl. J. Med. 2015; 372(26):2499–2508.
pHawkins C, et al. BRAF-KIAA1549 fusion predicts better clinical outcome in pediatric low-grade astrocytoma. Clin. Cancer Res. 2011; 17(14):4790–4798.
qKool M, et al. Molecular subgroups of medulloblastoma: an international meta-analysis of transcriptome, genetic aberrations, and clinical data of WNT, SHH, Group 3, and Group 4 medulloblastomas. Acta Neuropathol. 2012; 123(4):473–484.
rNorthcott PA, et al. Molecular subgroups of medulloblastoma. Expert Rev. Neurother. 2012; 12(7):871–884.
sNorthcott PA, et al. Medulloblastomics: the end of the beginning. Nat. Rev. Cancer. 2012; 12(12):818–834.
tNorthcott PA, et al. The whole-genome landscape of medulloblastoma subtypes. Nature. 2017; 547(7663):311–317.
uZhukova N, et al. Subgroup-specific prognostic implications of TP53 mutation in medulloblastoma. J. Clin. Oncol. 2013; 31(23):2927–2935.
vCeccom J, et al. Embryonal tumor with multilayered rosettes: diagnostic tools update and review of the literature. Clin. Neuropathol. 2014; 33(1):15–22.
wKorshunov A, et al. Embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma, and medulloepithelioma share molecular similarity and comprise a single clinicopathological entity. Acta Neuropathol. 2014; 128(2):279–289.
Abbreviations: SSF-Site-Specific Factor; SSDI-Site-Specific Data Item