Department of Hematology and Oncology, Mayo Clinic, Phoenix, Arizona, USA.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Neuro Oncol. 2023 Jan 5;25(1):28-36. doi: 10.1093/neuonc/noac205.
Isocitrate dehydrogenase (IDH) 1 or 2 mutations confer a favorable prognosis compared to IDH-wildtype in astrocytoma, frequently denoting a lower grade malignancy. However, recent molecular profiling has identified specific aggressive tumor subgroups with clear clinical prognostic implications that are independent of histologic grading. The homozygous deletion of CDKN2A/B is the strongest implicated independent indicator of the poor prognosis within IDH-mutant astrocytoma, and the identification of this alteration in these lower histologic grade tumors transforms their biology toward an aggressive grade 4 phenotype clinically. CDKN2A/B homozygous deletion is now sufficient to define a grade 4 tumor in IDH-mutant astrocytomas regardless of histologic appearance, yet there are currently no effective molecularly informed targeted therapies for these tumors. The biological impact of CDKN2A/B homozygous deletion in IDH-mutant tumors and the optimal treatment strategy for this molecular subgroup remains insufficiently explored. Here we review the current understanding of the translational significance of homozygous deletion of CDKN2A/B gene expression in IDH-mutant astrocytoma and associated diagnostic and therapeutic implications.
异柠檬酸脱氢酶（IDH）1 或 2 突变与 IDH 野生型相比，在星形细胞瘤中预后较好，常提示恶性程度较低。然而，最近的分子分析已经确定了具有明确临床预后意义的特定侵袭性肿瘤亚组，这些亚组与组织学分级无关。CDKN2A/B 的纯合缺失是 IDH 突变星形细胞瘤中预后不良的最强独立指标，在这些较低组织学分级的肿瘤中发现这种改变，使其生物学行为向侵袭性 4 级表型转变。CDKN2A/B 纯合缺失现在足以在 IDH 突变星形细胞瘤中定义为 4 级肿瘤，无论其外观如何，但目前针对这些肿瘤尚无有效的基于分子的靶向治疗方法。CDKN2A/B 纯合缺失在 IDH 突变肿瘤中的生物学影响以及针对该分子亚组的最佳治疗策略仍未得到充分探索。在这里，我们回顾了 CDKN2A/B 基因表达在 IDH 突变星形细胞瘤中的纯合缺失的转化意义及其相关诊断和治疗意义的现有认识。
