Brain Cancer Molecular Offering

Brain Cancer Molecular Offering

To provide the relevant diagnostic information for brain cancer patients and assist clinicians with effective patient management, GenPath offers a series of guidelines-based molecular assays for use in these clinical situations.

1p/19q Co-Deletion by FISH

TEST CODE: A311-3

1p/19q co-deletion is a well-established tumor cell-specific chromosomal abnormality in oligodendrogliomas.1

The combined loss of the 1p and 19q loci is a favorable prognostic indicator associated with good response to treatment and higher survival rates in gliomas. Whereas, polysomy of either chromosome 1 or
19 is associated with a less favorable outcome in oligodendrogliomas.2,3,4

MGMT Promoter Methylation by PCR

TEST CODE: J817-8

The MGMT gene encodes for a DNA repair enzyme that inhibits DNA damage caused by alkylating agents, resulting in tumor resistance.5 The methylation status of the MGMT promoter has been established as
an important clinical biomarker in glioblastoma and is of greatest interest in prognosti cation of newly diagnosed patients.6

In glioblastoma, the promoter methylation of the MGMT gene is an independent predictive factor of survival in patients undergoing chemotherapy with alkylating agents.6

IDH1/ IDH2 Sequencing by NGS

TEST CODE: J635-4

Isocitrate dehydrogenase (IDH) is an important metabolic enzyme involved in epigenetic modi cation. Together with 1p/19q co-deletion and MGMT promoter methylation, the presence of IDH1/ IDH2 mutations are a favorable prognostic marker associated with better survival for patients treated with radiation or alkylator chemotherapy, but not for untreated patients.5
OnkoSight NGS Glioma Panel (8 genes)

TEST CODE: J634-7

The OnkoSight NGS Glioma Panel consists of 8 genes that may have clinical actionability in brain tumors, especially as they relate to treatment selection in recurrent GBM patients.

Click on a gene below to learn more

BRAF – primarily associated with pediatric gliomas and detected in low-grade gliomas.12 National guidelines recommend testing for BRAF status for recurrent disease to determine potential use of BRAF inhibitors dabrafenib and vemurafenib.8
EGFR – associated with glioblastomas (GBM). EGFR is a tumor specific surface marker, widely used for targeted immunotherapy approaches.13 National guidelines recommend testing for EGFR status for recurrent GBM for consideration of EGFR-targeted therapies in some patients.8
IDH1/IDH2 – associated with Oligodendrogliomas and astrocytomas WHO grade II and III, secondary GBM.13 Co-deletion is a favorable prognostic indicator and survival benefit for patients treated with radiation or alkylator chemotherapy, but not in untreated patients. National Guidelines recommended; diagnostic for oligodendroglial histology.8
TP53 – associated with glioblastoma and astrocytoma. TP53 assists in the diagnosis of different subtypes of brain cancer.7
NRAS – associated with glioblastomas. mIR-340 negatively influences multiple aspects of glioblastoma tumorigenesis by down-regulating NRAS and downstream AKT and ERK pathways.14
PIK3CA – associated with glioblastomas. PIK3CA activation is associated with increasing tumor grade, decreased apoptosis and adverse clinical outcomes.15
PTEN – associated with glioblastomas, astrocytomas, and oligodendrogliomas. Detection of PTEN gene alteration in Pten/PI3K/Akt pathway genes is a negative prognostic marker, but may show selective susceptibility to Pten/PI3K/Akt pathway inhibitors.16
KEY BENEFITS

Cost-effective, targeted, and actionable
Requires minimal FFPE DNA input requirements (as low as 0.5 ng)
Rapid turnaround time (TAT) of 5-10 days from receipt of the specimen in our laboratory

References

  1. Jiang H, Zhang Z, Ren X et al., Tumor cell-speci c chromosomal abnormality in the vascular endothelial cells of anaplastic oligodendroglioma J Neurosurg 2016 Oct; 125(4):995-1001. Epub 2016 Jan 15.
  2. Jenkins RB, Blair H, Ballman KV, et al. A t(1;19)(q10;p10) Mediates the Combined Deletions of 1p and 19q and Predicts a Better Prognosis of Patients with Oligodendroglioma. Cancer Research 66(20):9852-9861,2006.
  3. Sennetta R. Verdun di Cantogno L, Chiusa L, et al. A “Weighed” Flourescence in Situ Hybridization Strengthens the Favorable Prognostic Value of 1p/19q Codeletion in Pure and Mixed Oligodendrogial Tumors. J Neuropathol Exp Neurol 72(5):432-441,2013.
  4. Snuderl M, Eichler A, Ligon KL, et al. Polysomy for Chromosomes 1 and 19 Predicts Earlier recurrence in Anaplastic Oligodendrogliomas with Concurrent 1p/19q Loss. Clin Cancer Res 15 (20):6430-6437,2009.
  5. Principles of Brain Tumor Pathology, National Guidelines Central Nervous System Cancers version 1.2017
  6. Niklas T, Simone K, Friedrich WK, Personalized Treatment Strategies in Glioblastoma: MGMT promoter methylation status, Onco Targets Ther. 2016; 6:
    1363-1372 Published online 2013 Sept 27
  7. Sung-Hye P, Jaekyung W, Seong-Ik et al., Molecular Testing of Brain Tumor J Pathology Transl Med 2017; 51: 205-223
  8. Verena S, Omar DD, Matthias H, Actionable Molecular Biomarkers in Primary Brain Tumors, Trends Cancer Author Manuscript; available in PMC 2017 July 01
  9. Danilo F. Elvira D, Giuseppinna R et al., miR-340 predicts glioblastoma survival and modulates key cancer hallmarks through down- regulation of NRAS, Oncotarget vol 7 no 15, Published January 21, 2016
  10. Arnab C, Gary Z, Yoshiyuki S et al, The Prognostic Signi cance of Phosphatidylinositol 3-Kinase Pathway Activation in Human Gliomas, Journal of Clinical Oncology Vol 22 number
  11. Christiane BK, Adrian M, Guido R PTEN Signaling in Gliomas, Neuro-Oncology July 2002
  12. Craig H, Marina NN, Jill MH eta al., Interplay among BRAF, p16, p53, and M1B1 in pediatric low-grade gliomas, Neuro-Oncology 14(6):777-789, 2012, DOI:10.1093/neuonc/nos077