FISH analysis reveals CDKN2A and IFNA14 co-deletion is heterogeneous and is a prominent feature of glioblastoma

IF 2.7 3区医学 Q2 CLINICAL NEUROLOGY Brain Tumor Pathology Pub Date : 2023-12-14 DOI:10.1007/s10014-023-00473-6

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Abstract

Deletion of CDKN2A occurs in 50% of glioblastomas (GBM), and IFNA locus deletion in 25%. These genes reside closely on chromosome 9. We investigated whether CDKN2A and IFNA were co-deleted within the same heterogeneous tumour and their prognostic implications. We assessed CDKN2A and IFNA14 deletions in 45 glioma samples using an in-house three-colour FISH probe. We examined the correlation between p16^INK4a protein expression (via IHC) and CDKN2A deletion along with the impact of these genomic events on patient survival. FISH analyses demonstrated that grades II and III had either wildtype (wt) or amplified CDKN2A/IFNA14, whilst 44% of GBMs harboured homozygous deletions of both genes. Cores with CDKN2A homozygous deletion (n = 11) were negative for p16^INK4a. Twenty p16^INK4a positive samples lacked CDKN2A deletion with some of cells showing negative p16^INK4a. There was heterogeneity in IFNA14/CDKN2A ploidy within each GBM. Survival analyses of primary GBMs suggested a positive association between increased p16^INK4a and longer survival; this persisted when considering CDKN2A/IFNA14 status. Furthermore, wt (intact) CDKN2A/IFNA14 were found to be associated with longer survival in recurrent GBMs. Our data suggest that co-deletion of CDKN2A/IFNA14 in GBM negatively correlates with survival and CDKN2A-wt status correlated with longer survival, and with second surgery, itself a marker for improved patient outcomes.

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FISH 分析显示 CDKN2A 和 IFNA14 共同缺失具有异质性，是胶质母细胞瘤的一个显著特征

摘要 50%的胶质母细胞瘤（GBM）发生 CDKN2A 基因缺失，25%发生 IFNA 基因座缺失。这些基因紧密位于第 9 号染色体上。我们研究了 CDKN2A 和 IFNA 是否在同一异质性肿瘤中共同缺失及其对预后的影响。我们使用内部三色 FISH 探针评估了 45 个胶质瘤样本中 CDKN2A 和 IFNA14 的缺失情况。我们研究了 p16INK4a 蛋白表达（通过 IHC）与 CDKN2A 基因缺失之间的相关性，以及这些基因组事件对患者生存的影响。FISH 分析表明，II 级和 III 级患者的 CDKN2A/IFNA14 要么是野生型（wt），要么是扩增型，而 44% 的 GBM 则同时存在这两个基因的同源缺失。CDKN2A同源缺失的核心（n = 11）p16INK4a呈阴性。20 个 p16INK4a 阳性样本缺乏 CDKN2A 基因缺失，其中一些细胞 p16INK4a 阴性。每个 GBM 中的 IFNA14/CDKN2A 倍体存在异质性。原发性 GBM 的存活率分析表明，p16INK4a 增加与存活期延长呈正相关；当考虑到 CDKN2A/IFNA14 状态时，这种关系依然存在。此外，在复发性 GBM 中，CDKN2A/IFNA14 的 wt（完整）与较长的存活期相关。我们的数据表明，GBM 中 CDKN2A/IFNA14 共缺失与生存率呈负相关，CDKN2A-wt 状态与较长的生存率和二次手术相关，而二次手术本身就是改善患者预后的标志。

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来源期刊

Brain Tumor Pathology 医学-病理学

CiteScore

5.40

自引率

9.10%

发文量

审稿时长

>12 weeks

期刊介绍： Brain Tumor Pathology is the official journal of the Japan Society of Brain Tumor Pathology. This international journal documents the latest research and topical debate in all clinical and experimental fields relating to brain tumors, especially brain tumor pathology. The journal has been published since 1983 and has been recognized worldwide as a unique journal of high quality. The journal welcomes the submission of manuscripts from any country. Membership in the society is not a prerequisite for submission. The journal publishes original articles, case reports, rapid short communications, instructional lectures, review articles, letters to the editor, and topics.Review articles and Topics may be recommended at the annual meeting of the Japan Society of Brain Tumor Pathology. All contributions should be aimed at promoting international scientific collaboration.