目的:胶质瘤是来源于脑内多种细胞类型的高度异质性恶性肿瘤。虽然他们的确切病因往往是未知的,危险因素,例如化学暴露,辐射,和特定的不常见的遗传疾病已经确定。诊断通常需要影像学检查,如磁共振成像和计算机断层扫描,辅以活检确认,这可以通过基因检测进一步验证。
方法:下一代测序技术揭示了根据肿瘤的分子特征诊断为多形性黄色星形细胞瘤的患者中细胞周期蛋白依赖性激酶抑制剂2A和B基因(CDKN2A和CDKN2B)的种系共缺失。根据这个结果,我们使用多重连接依赖性探针扩增技术对显示相同共缺失的母亲进行了集中的遗传分析.此外,由于父亲的神经内分泌胰腺癌,NGS技术的应用在BRCA1相互作用解旋酶1(BRIP1)基因中检测到致病性变异。在家族背景下进行的综合多基因检测,以各种各样的癌症类型为标志,揭示了一系列遗传倾向。
结论:本案例研究强调了分子检测对肿瘤特征的重要性,并强调了基因检测在促进早期干预和筛查高危家庭成员中的关键作用。此外,癌症种系共缺失的鉴定为制定旨在恢复正常细胞调节和改善患者管理的靶向治疗策略奠定了基础.
OBJECTIVE: Gliomas are highly heterogeneous malignancies originating from diverse cell types within the brain. Although their precise etiology is frequently unknown, risk factors, such as chemical exposure, radiation, and specific uncommon genetic disorders have been identified. Diagnosis typically entails imaging tests, such as magnetic resonance imaging and computed tomography, complemented by a biopsy for confirmation, which may be further validated through genetic testing.
METHODS: Next-generation sequencing technology revealed germline co-deletion deletion of cyclin-dependent kinase inhibitor 2 A and B genes (CDKN2A and CDKN2B) in a patient diagnosed with pleomorphic xanthoastrocytoma based on the tumor\'s molecular characteristics. Following this result, we performed focused genetic analysis with use of multiplex ligation-dependent probe amplification technology for the mother that revealed the same co-deletion. Moreover, due to the father\'s neuroendocrine pancreatic cancer, application of the NGS technology detected a pathogenic variant in the BRCA1-interacting helicase 1 (BRIP1) gene. Comprehensive multi-gene testing conducted within the familial context, marked by a varied spectrum of cancer type, revealed a constellation of genetic predispositions.
CONCLUSIONS: This case study underscores the critical importance of molecular testing for tumor characterization and highlights the pivotal role of genetic testing in facilitating early intervention and screening for at-risk family members. Furthermore, the identification of germline co-deletions in cancer lays the foundation for the development of targeted therapeutic strategies aimed at restoring normal cellular regulation and improving patient management.