AANS 2017: Genetic Underpinnings of Desmoplastic Infantile Ganglioglioma/Astrocytoma

Key Points

  • Researchers identified a subset of DIG/DIAs harboring BRAF mutations with approximately a 48.3% frequency.
  • While a specific type of BRAF alteration, the BRAF V600D mutation, has, to this point, proven exceedingly rare, this study revealed 3 among 16 total DIG/DIAs.
  • The authors also identified incomplete resection, DIA pathology, multifocal disease at presentation, and malignant transformation as independent predictors of poor outcome in DIG/DIA patients.

Winner of the American Brain Tumor Association Young Investigator Award Anthony C. Wang, MD, a neurosurgeon at the University of California Los Angeles (UCLA) Mattel Children’s Hospital and the David Geffen School of Medicine at UCLA, presented his research findings on desmoplastic infantile ganglioglioma/astrocytoma during the 2017 American Association of Neurological Surgeons (AANS) Annual Scientific Meeting. His research was made possible through a multinational collaboration between researchers and physicians in Seattle, Toronto, and Heidelberg.

The World Health Organization (WHO) classifies desmoplastic infantile ganglioglioma (DIG) and desmoplastic infantile astrocytoma (DIA) together among benign grade I brain tumors. Typically found in young children, these rare malignancies have an excellent prognosis when completely removed through surgery.

Dr. Wang and his research collaborators aimed to understand genetic underpinnings of DIG/DIA and their natural histories. Advanced DNA sequencing techniques (UW-OncoPlex) and DNA methylation profiling were performed on specimens obtained from 16 patients diagnosed with DIG/DIA. The team also performed an exhaustive individual patient data meta-analysis of previously reported cases of DIG/DIA.

Genetic Findings

Among the 16 original tumor samples, the authors unexpectedly identified a subset of DIG/DIAs harboring BRAF mutations with approximately a 48.3% frequency. Although the BRAF V600E mutation, a specific type of BRAF alteration, has historically proven to be exceedingly rare, this study revealed 3 among the 16 total DIG/DIAs. No other oncogenic mutation has been consistently identified in DIG/DIAs.

The authors also identified incomplete resection, DIA pathology, multifocal disease at presentation, and malignant transformation as independent predictors of poor outcome in DIG/DIA patients. Malignant transformation was identified in 33.3% of patients, much higher than previously recognized, and the interval development of new mutations drove these cases of malignant transformation.

Maximal safe resection remains the mainstay of treatment for these tumors. However, Dr. Wang and his colleagues highlight the need to test all DIG/DIA for BRAF and other gene mutations, which might uncover alternative treatment options, such as BRAF inhibitors in cases where the tumor is unable to be completely removed.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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