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Abstract：
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.
摘要：
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。室管膜瘤通常对化学疗法难以治疗，因此缺乏任何有效的治疗方法。这里,我们报道了CXorf67（染色体X开放阅读框67）的表达升高，经常发生在PFA室管膜瘤中，抑制同源重组（HR）介导的DNA修复。机械上,CXorf67与PALB2相互作用并抑制PALB2-BRCA2相互作用，从而抑制HR修复。和谐地，具有高CXorf67表达水平的肿瘤细胞显示对聚（ADP-核糖）聚合酶（PARP）抑制剂的敏感性增加，特别是与放疗结合使用时。因此，我们的研究结果揭示了CXorf67在HR修复中的作用,并提示PARP抑制剂联合放疗可能是PFA室管膜瘤的有效治疗选择.
