Grebstad Tune Benedicte, Sareen Heena, Powter Branka, Kahana-Edwin Smadar, Cooper Adam, Koh Eng-Siew, Lee Cheok S, Po Joseph W, McCowage Geoff, Dexter Mark, Cain Lucy, O'Neill Geraldine, Prior Victoria, Karpelowsky Jonathan, Tsoli Maria, Baumbusch Lars O, Ziegler David, Roberts Tara L, DeSouza Paul, Becker Therese M, Ma Yafeng
Department of Pediatric Research, Division of Paediatric and Adolescent Medicine, Oslo University Hospital Rikshospitalet, 0372 Oslo, Norway.
Institute of Clinical Medicine, University of Oslo, 0318 Oslo, Norway.
Biomedicines. 2023 Oct 27;11(11):2907. doi: 10.3390/biomedicines11112907.
Genetic histone variants have been implicated in cancer development and progression. Mutations affecting the histone 3 (H3) family, H3.1 (encoded by and ) and H3.3 (encoded by ), are mainly associated with pediatric brain cancers. While considered poor prognostic brain cancer biomarkers in children, more recent studies have reported H3 alterations in adult brain cancer as well. Here, we established reliable droplet digital PCR based assays to detect three histone mutations (H3.3-K27M, H3.3-G34R, and H3.1-K27M) primarily linked to childhood brain cancer. We demonstrate the utility of our assays for sensitively detecting these mutations in cell-free DNA released from cultured diffuse intrinsic pontine glioma (DIPG) cells and in the cerebral spinal fluid of a pediatric patient with DIPG. We further screened tumor tissue DNA from 89 adult patients with glioma and 1 with diffuse hemispheric glioma from Southwestern Sydney, Australia, an ethnically diverse region, for these three mutations. No histone mutations were detected in adult glioma tissue, while H3.3-G34R presence was confirmed in the diffuse hemispheric glioma patient.
遗传组蛋白变体与癌症的发生和发展有关。影响组蛋白3（H3）家族、H3.1（由 和 编码）和H3.3（由 编码）的突变主要与儿童脑癌相关。虽然这些突变在儿童脑癌中被认为是预后不良的生物标志物，但最近的研究也报道了成人脑癌中存在H3改变。在此，我们建立了基于可靠的液滴数字PCR的检测方法，以检测三种主要与儿童脑癌相关的组蛋白突变（H3.3-K27M、H3.3-G34R和H3.1-K27M）。我们证明了我们的检测方法在灵敏检测从培养的弥漫性固有桥脑胶质瘤（DIPG）细胞释放的游离DNA以及一名患有DIPG的儿科患者的脑脊液中的这些突变方面的实用性。我们进一步筛查了来自澳大利亚悉尼西南部一个种族多样地区的89名成年胶质瘤患者和1名弥漫性半球胶质瘤患者的肿瘤组织DNA中的这三种突变。在成人胶质瘤组织中未检测到组蛋白突变，而在弥漫性半球胶质瘤患者中证实存在H3.3-G34R突变。
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