FGFR3::TACC3fusion is a driver, potentially targetable, genetic alteration identified in approximately 4% of high-grade diffuse gliomas and rare cases with low-grade histology. Herein, we review the genetic and epigenetic features of these tumors and highlight the challenges in their classification and grading. Diffuse gliomas withFGFR3::TACC3fusion display unique histopathological and molecular features, including an oligodendroglioma-like appearance, calcifications, and CD34 extravascular immunoreactivity. High-grade tumors exhibit molecular alterations and a DNA methylation profile typical of glioblastoma, suggesting that they may represent a subtype clinically characterized by a slightly better prognosis. Tumors with low-grade morphology are genetically and epigenetically heterogeneous. Some, exclusive to adults, have molecular alterations typical of glioblastoma, although most do not match any methylation classes, using version 12.5 of the Heidelberg classifier. Another group, which mostly affects children or adolescents, lacks the molecular features of glioblastoma and has a DNA methylation profile similar to that of low-grade glioneuronal tumors. In conclusion, diffuse gliomas withFGFR3::TACC3fusion do not constitute a distinct nosological entity, owing to their genetic and epigenetic diversity. Further studies are warranted to clarify the biological aggressiveness of tumors with low-grade histology to refine the grading and determine the optimal treatment strategy.
FGFR3::TACC3融合是一种驱动性且潜在可靶向的遗传变异，约见于4%的高级别弥漫性胶质瘤及少数低级别组织学病例。本文综述了此类肿瘤的遗传学与表观遗传学特征，并重点探讨其分类与分级所面临的挑战。携带FGFR3::TACC3融合的弥漫性胶质瘤具有独特的组织病理学和分子特征，包括少突胶质细胞瘤样形态、钙化及CD34血管外免疫反应性。高级别肿瘤呈现典型的胶质母细胞瘤分子改变及DNA甲基化谱，提示其可能代表一种临床预后稍好的亚型。具有低级别形态的肿瘤在遗传和表观遗传层面存在异质性：其中部分仅发生于成人，虽具有胶质母细胞瘤典型分子改变，但大多数不符合海德堡分类器12.5版中的任何甲基化类别；另一组主要累及儿童或青少年，缺乏胶质母细胞瘤分子特征，其DNA甲基化谱与低级别胶质神经元肿瘤相似。综上所述，由于遗传和表观遗传的多样性，携带FGFR3::TACC3融合的弥漫性胶质瘤并不构成独立的疾病实体。需要进一步研究明确低级别组织学肿瘤的生物学侵袭性，以完善分级体系并确定最佳治疗策略。
肿瘤(癌症)患者之家