Ependymoma is the third most common pediatric tumor with posterior fossa group A (PFA) being its most aggressive subtype. Ependymomas are generally refractory to chemotherapies and thus lack any effective treatment. Here, we report that elevated expression of CXorf67 (chromosome X open reading frame 67), which frequently occurs in PFA ependymomas, suppresses homologous recombination (HR)-mediated DNA repair. Mechanistically, CXorf67 interacts with PALB2 and inhibits PALB2-BRCA2 interaction, thereby inhibiting HR repair. Concordantly, tumor cells with high CXorf67 expression levels show increased sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors, especially when combined with radiotherapy. Thus, our findings have revealed a role of CXorf67 in HR repair and suggest that combination of PARP inhibitors with radiotherapy could be an effective treatment option for PFA ependymomas.

室管膜瘤是第三大最常见的儿科肿瘤，后颅窝 A 组 (PFA) 是其最具侵袭性的亚型。室管膜瘤通常对化疗无效，因此缺乏任何有效的治疗方法。在这里，我们报告了经常发生在 PFA 室管膜瘤中的 CXorf67（染色体 X 开放阅读框 67）的表达升高，抑制了同源重组 (HR) 介导的 DNA 修复。从机制上讲，CXorf67 与 PALB2 相互作用并抑制 PALB2-BRCA2 相互作用，从而抑制 HR 修复。同时，具有高 CXorf67 表达水平的肿瘤细胞对聚（ADP-核糖）聚合酶 (PARP) 抑制剂的敏感性增加，尤其是在与放疗联合使用时。因此，