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The Evolving Molecular Genetics of Low-grade Glioma

Venneti, Sriram MD, PhD*; Huse, Jason T. MD, PhD


In the article “The Evolving Molecular Genetics of Low-grade Glioma” in the March 2015 issue of Advances in Anatomic Pathology on pages 94–101, the figure legends were mistakenly switched.

The legends should have been listed as follows:

FIGURE 1. FGFR1 and BRAF alterations in pediatric low-grade glioma (LGG) converge on the mitogen-activated protein (MAP) kinase pathway. Alterations in FGFR1 result in constitutive activation of the receptor resulting in activation of the MAP kinase pathway. A subset of pediatric LGG also shows mutations in the receptor tyrosine kinase NTRK2 . Rare mutations involve other members of this pathway including RAS , NF1 (negative regulator of RAS), and PTPN11 , a tyrosine phosphatase adapter protein. BRAF V600E mutations and the BRAF-KIAA1549 fusion (other rare fusions not illustrated) also result in constitutive kinase activity and aberrant MAP kinase activation. Please see this image in color online.

FIGURE 2. IDH 1/2 , ATRX , and TERT promoter mutations and 1p/19q codeletion in adult low-grade glioma (LGG). IDH 1/2 mutations are thought to be an early event in adult LGG pathogenesis in a common precursor cell. Mutations in IDH1 (cytoplasmic) and IDH2 (mitochondrial) result in the generation of the oncometabolite 2-hydroxyglutarate (2HG). 2HG is thought to inhibit aketoglutarate-dependent demethylases resulting in histone and DNA-CpG island methylation (G-CIMP phenotype). Mutations in ATRX are seen in astrocytic tumors. ATRX is a helicase belonging to the SWItch/Sucrose NonFermentable family involved in H3.3 deposition (along with its partner DAXX). Its deficiency induces alternative lengthening of telomeres. 1p/19q codeletion is seen in oligodendrogliomas. CIC and FUBP1 alterations are associated with 1p/19q codeletion in a variable percentage of oligodendrogliomas. TERT promoter mutations are also noted in oligodendrogliomas and are thought to be important for telomere maintenance. Please see this image in color online.

Advances in Anatomic Pathology. 22(3):226, May 2015.

Advances In Anatomic Pathology: March 2015 - Volume 22 - Issue 2 - p 94–101
doi: 10.1097/PAP.0000000000000049
Review Articles

Low-grade gliomas (LGG) constitute grades I and II tumors of astrocytic and grade II tumors of oligodendroglial lineage. Although these tumors are typically slow growing, they may be associated with significant morbidity and mortality because of recurrence and malignant progression, even in the setting of optimal resection. LGG in pediatric and adult age groups are currently classified by morphologic criteria. Recent years have heralded a molecular revolution in understanding brain tumors, including LGG. Next-generation sequencing has definitively demonstrated that pediatric and adult LGG fundamentally differ in their underlying molecular characteristics, despite being histologically similar. Pediatric LGG show alterations in FGFR1 and BRAF in pilocytic astrocytomas and FGFR1 alterations in diffuse astrocytomas, each converging on the mitogen-activated protein kinase signaling pathway. Adult LGG are characterized by IDH1/2 mutations and ATRX mutations in astrocytic tumors and IDH1/2 mutations and 1p/19q codeletions in oligodendroglial tumors. TERT promoter mutations are also noted in LGG and are mainly associated with oligodendrogliomas. These findings have considerably refined approaches to classifying these tumors. Moreover, many of the molecular alterations identified in LGG directly impact on prognosis, tumor biology, and the development of novel therapies.

*Department of Pathology, Division of Neuropathology, University of Michigan Medical School, Ann Arbor, MI

Department of Pathology and Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY

S.V. is supported by NCI-K08 CA181475.

The authors have no conflicts of interest to disclose.

Reprints: Jason T. Huse, MD, PhD, Department of Pathology and Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, 408 E 69th Street (Z701), New York, NY 10065 (e-mail:

All figures can be viewed online in color at

© 2015 by Lippincott Williams & Wilkins.