Lower Grade Glioma Study

What is lower grade glioma?

Glioma is a type of cancer that develops in the glial cells of the brain. Glial cells support the brain’s nerve cells and keep them healthy. Tumors are classified into grades I, II, III or IV based on standards set by the World Health Organization. For this study, TCGA studied lower grade glioma, which consists of grades II and III. Regardless of grade, as a glioma tumor grows, it compresses the normal brain tissue, frequently causing disabling or fatal effects.¹ In 2010, more than 22,000 Americans were estimated to have been diagnosed and 13,140 were estimated to have died from brain and other nervous system cancers.² Additional information on brain tumors.

What have TCGA researchers learned about lower grade glioma?

• Mutations and chromosomal alterations define three lower grade glioma subtypes with distinct clinical outcomes: 
  • IDH mutant and 1p/19q co-deletion:
    • The 1p/19q abnormality consists of deletion of a short arm of chromosome 1 and longer arm of chromosome 19.
    • Mutations in IDH1 and IDH2, isocitrate dehydrogenases, lead to abnormal enzyme activity, hypermethylation, and deviant gene expression.
    • This subtype is associated with the most favorable prognosis.
  • IDH mutant without 1p/19q co-deletion, associated with intermediate prognosis
  • IDH wild-type, associated with the poorest outcomes
• IDH wild-type subtype shares genomic markers and similar clinical outcomes with glioblastomas, indicating that this subtype of lower grade glioma may be a precursor to the more aggressive counterpart.
• Molecular signatures and subtypes may inform the classification, diagnosis, and treatment of lower grade gliomas:
  • Lower grade gliomas without IDH mutations may benefit from treatment with protocols adapted from current glioblastoma treatments.
  • Recently developed therapies may target the aberrant activity of IDH1/2 proteins in lower grade glioma.