在低级别（世界卫生组织II - III级）星形细胞瘤中，CDKN2A缺失与总生存期缩短相关。
CDKN2A loss is associated with shortened overall survival in lower-grade (World Health Organization Grades II-III) astrocytomas.
作者信息
Reis Gerald F, Pekmezci Melike, Hansen Helen M, Rice Terri, Marshall Roxanne E, Molinaro Annette M, Phillips Joanna J, Vogel Hannes, Wiencke John K, Wrensch Margaret R, Walsh Kyle M, Perry Arie
机构信息
From the Departments of Neurology, Pediatrics, and Neurosurgery, Stanford University School of Medicine, Stanford (HV); Department of Anatomic Pathology, University of California San Francisco Medical School (GFR, MP, AP); Division of Neuroepidemiology (HMH, TR, JKW, MRW, KMW), Departments of Neurological Surgery (REM, AMM, JJP, AP) and Epidemiology and Biostatistics (AMM); and Institute for Human Genetics, University of California San Francisco (JKW, MRW, KMW), San Francisco, California.
出版信息
J Neuropathol Exp Neurol. 2015 May;74(5):442-52. doi: 10.1097/NEN.0000000000000188.
Lower-grade (World Health Organization Grades II and III) gliomas vary widely in clinical behavior and are classified as astrocytic, oligodendroglial, or mixed. Anaplasia depends greatly on mitotic activity, with CDKN2A loss considered as the most common mechanism for cell cycle dysregulation. We investigated whether loss of the CDKN2A gene is associated with overall survival across pathologically and genetically defined glioma subtypes. After adjustment for IDH mutation, sex, and age, CDKN2A deletion was strongly associated with poorer overall survival in astrocytomas but not in oligodendrogliomas or oligoastrocytomas. Molecular classification of astrocytomas by IDH mutation, TP53 mutation, and /or ATRX loss of expression revealed that CDKN2A loss in IDH/TP53 mutated tumors was strongly associated with worse overall survival. CDKN2A loss in IDH mutated tumors with ATRX loss was only weakly associated with worse overall survival. These findings suggest that CDKN2A testing may provide further clinical aid in lower-grade glioma substratification beyond IDH mutation and 1p19q codeletion status, particularly in IDH/TP53 mutated astrocytomas.
低级别（世界卫生组织二级和三级）胶质瘤的临床行为差异很大，分为星形细胞型、少突胶质细胞型或混合型。间变在很大程度上取决于有丝分裂活性，CDKN2A缺失被认为是细胞周期失调的最常见机制。我们研究了CDKN2A基因缺失是否与病理和基因定义的胶质瘤亚型的总生存期相关。在调整了异柠檬酸脱氢酶（IDH）突变、性别和年龄后，CDKN2A缺失与星形细胞瘤患者较差的总生存期密切相关，但与少突胶质细胞瘤或少突星形细胞瘤无关。通过IDH突变、TP53突变和/或ATRX表达缺失对星形细胞瘤进行分子分类，结果显示IDH/TP53突变肿瘤中的CDKN2A缺失与更差的总生存期密切相关。IDH突变且伴有ATRX缺失的肿瘤中，CDKN2A缺失仅与较差的总生存期有微弱关联。这些发现表明，CDKN2A检测可能在低级别胶质瘤分层中提供超出IDH突变和1p19q共缺失状态的进一步临床帮助，特别是在IDH/TP53突变的星形细胞瘤中。
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