Integrating molecular analyses with the 2021 WHO classification of adult pilocytic astrocytomas.

in Journal of neuropathology and experimental neurology by Beatriz Moreno-Torres, Irene Manzano-Benito, Diana Cantero, Ángel Romo, Ángel Rodríguez de Lope, Manuela Mollejo, Aurelio Hernández-Laín, Bárbara Meléndez

TLDR

  • The study investigated the molecular characteristics of adult pilocytic astrocytomas and found that the K-B fusion was a frequent alteration, which did not correlate with poor outcome.

Abstract

Pilocytic astrocytomas (PAs) are benign grade 1 gliomas according to the World Health Organization (WHO). They are common in children but rare in adults in whom they may have a worse prognosis. Pediatric PAs are usually associated with dysregulation of the mitogen-activated protein kinase (MAPK) pathway, often involving BRAF alterations such as the KIAA1549::BRAF (K-B) fusion or V600E mutation. We investigated the molecular characteristics of adult PA using gene-targeted next-generation sequencing and specific gene tests, including for K-B fusion, TERT promoter, and FGFR1 hotspot mutations. The most frequent molecular alterations detected involved the MAPK pathway, particularly affecting BRAF and NF1 genes (55%). The prevalence of the K-B fusion (>40%) was higher than previously reported, likely due to challenges in detecting it. We identified molecular alterations in some cases that raised the differential diagnosis of other tumor types, revealing limitations in the 2021 WHO classification for adult PA. After removing other diagnostic types that may mimic PA histology, no adult patients with a diagnosis of PA and K-B fusion died after more than 10 years of mean follow-up. These findings suggest that, similar to pediatric cases, PA in adults may be driven by a single molecular hit, where the K-B fusion is not related to poor outcome.

Overview

  • The study investigated the molecular characteristics of adult pilocytic astrocytomas (PAs) using gene-targeted next-generation sequencing and specific gene tests.
  • The study used gene-targeted next-generation sequencing and specific gene tests to investigate the molecular characteristics of adult PAs, including the K-B fusion, TERT promoter, and FGFR1 hotspot mutations.
  • The primary objective of the study was to identify the molecular alterations that drive the development and progression of adult PAs and to assess their impact on patient outcomes.

Comparative Analysis & Findings

  • The study found that the most frequent molecular alterations in adult PAs involved the MAPK pathway, particularly affecting BRAF and NF1 genes, which was 55% of the cases.
  • The prevalence of the K-B fusion was higher than previously reported, which was above 40% of the cases.
  • The study identified molecular alterations in some cases that raised the differential diagnosis of other tumor types, revealing limitations in the 2021 WHO classification for adult PAs.

Implications and Future Directions

  • The study's findings suggest that, similar to pediatric cases, PA in adults may be driven by a single molecular hit, where the K-B fusion is not related to poor outcome.
  • The study highlights the need for further research to better understand the molecular mechanisms underlying adult PAs and to develop effective targeted therapies.
  • The study's findings also emphasize the importance of conducting additional diagnostic tests to rule out other tumor types that may mimic PA histology.
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