Chen Dongting, Ye Ling, Yu Zaitao, Lei Ting, Wang Yulin, Qu Zheng, Zhou Zhongqing, Lv Jiacheng, Liu Fangjun, Li Yan
Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, 100093, China.
J Neurooncol. 2025 Oct;175(1):35-46. doi: 10.1007/s11060-025-05061-6. Epub 2025 Jul 29.
Adamantinomatous craniopharyngioma (ACP) is a benign but surgically challenging intracranial tumor, and its high postoperative recurrence rate poses a threat to patient prognosis. In this study, whole exome sequencing (WES) was performed to comprehensively understand the genomic alterations in ACP.
First, the gene mutation profile of ACP was acquired through an overview of the WES data. The somatic single nucleotide variants (SNV) mutational spectrum and signature of ACP were analyzed. Subsequently, somatic mutation data were used to identify the characteristic SNV of recurrent ACP to further explore the mechanism underlying recurrence, and the effect of these mutations on protein expression was verified through immunohistochemical and immunofluorescence analyses.
We obtained the overall mutational landscape of ACP and identified four key mutated genes in recurrent samples: Procollagen-Lysine,2-Oxoglutarate 5-Dioxygenase 3 (PLOD3), Collagen Type XVII Alpha 1 chain (COL17A1), Fibronectin 1 (FN1), and Laminin Subunit Beta 3 (LAMB3). Among these, we verified that COL17A1, FN1, and LAMB3 expression was mainly located in the keratin nodule structures in tumors and was elevated in recurrent cases.
PLOD3, COL17A1, FN1, and LAMB3 were identified as the key mutated genes in recurrent samples. These findings could provide a new perspective for understanding the tumorigenesis and recurrence mechanisms of ACP. A deeper exploration is needed to determine whether these key mutated genes promote ACP recurrence and drive the overproduction of keratin nodules in recurrent cases.
成釉细胞瘤型颅咽管瘤（ACP）是一种良性但手术具有挑战性的颅内肿瘤，其高术后复发率对患者预后构成威胁。在本研究中，进行了全外显子组测序（WES）以全面了解ACP中的基因组改变。
首先，通过对WES数据的概述获取ACP的基因突变谱。分析了ACP的体细胞单核苷酸变异（SNV）突变谱和特征。随后，利用体细胞突变数据鉴定复发性ACP的特征性SNV，以进一步探索复发的潜在机制，并通过免疫组织化学和免疫荧光分析验证这些突变对蛋白质表达的影响。
我们获得了ACP的总体突变图谱，并在复发性样本中鉴定出四个关键突变基因：脯氨酸赖氨酸2-氧代戊二酸5-双加氧酶3（PLOD3）、 XVII型胶原蛋白α1链（COL17A1）、纤连蛋白1（FN1）和层粘连蛋白β3亚基（LAMB3）。其中，我们验证了COL17A1、FN1和LAMB3的表达主要位于肿瘤中的角质结节结构中，并且在复发病例中升高。
PLOD3、COL17A1、FN1和LAMB3被鉴定为复发性样本中的关键突变基因。这些发现可为理解ACP的肿瘤发生和复发机制提供新的视角。需要进行更深入的探索，以确定这些关键突变基因是否促进ACP复发并导致复发病例中角质结节的过度产生。
