Cancer cells often express differentiation programs unrelated to their tissue of origin, although the contribution of these aberrant phenotypes to malignancy is poorly understood. An aggressive subgroup of medulloblastoma, a malignant pediatric brain tumor of the cerebellum, expresses a photoreceptor differentiation program normally expressed in the retina. We establish that two photoreceptor-specific transcription factors, NRL and CRX, are master regulators of this program and are required for tumor maintenance in this subgroup. Beyond photoreceptor lineage genes, we identify BCL-XL as a key transcriptional target of NRL and provide evidence substantiating anti-BCL therapy as a rational treatment opportunity for select MB patients. Our results highlight the utility of studying aberrant differentiation programs in cancer and their potential as selective therapeutic vulnerabilities.

中文翻译：

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NRL和CRX定义了髓母细胞瘤中的感光受体身份并揭示了亚组特异性依赖性。

癌细胞通常表达与其起源组织无关的分化程序，尽管对这些异常表型对恶性肿瘤的贡献知之甚少。髓母细胞瘤的侵略性亚组是小脑的恶性小儿脑肿瘤，它表达通常在视网膜中表达的感光细胞分化程序。我们建立了两个感光受体特异性转录因子，NRL和CRX，是该程序的主要调控因子，并且是该亚组中肿瘤维持所必需的。除感光细胞谱系基因外，我们还将BCL-XL鉴定为NRL的关键转录靶标，并提供证实抗BCL治疗作为某些MB患者合理治疗机会的证据。