PDF(Pubmed)
Abstract：
Nuclear protein in testis (NUT) carcinoma is a rare but highly aggressive carcinoma, driven by genetic rearrangement of the NUT midline carcinoma family member 1 (NUTM1) gene on chromosome 15q14. Recently, a tight link has been suggested between genetic abnormalities and subsequent metabolic and epigenetic dysregulation to drive the progression of malignant tumors. However, it remains elusive whether such reprogramming could contribute to the pathogenesis of NUT carcinoma. We herein report an autopsy case of NUT carcinoma arising in the retroperitoneum of a 31-year-old male. Notably, reprogramming of glycolytic metabolism and epigenetic histone modifications was observed in this unusual NUT carcinoma case, and this phenomenon was further confirmed by an in vitro cell culture model with bromodomain containing 4 (BRD4)-NUT overexpression. The rationale for documenting the case is based on our findings to reveal that metabolic and epigenetic reprogramming could be one of the contributing factors to the pathogenesis of NUT carcinoma, which could be exploitable as a novel therapeutic target for this rare and aggressive cancer type.
摘要：
睾丸中的核蛋白（NUT）癌是一种罕见但高度侵袭性的癌，由染色体15q14上的NUT中线癌家族成员1（NUTM1）基因的遗传重排驱动。最近,遗传异常与随后的代谢和表观遗传失调之间存在紧密的联系，从而驱动恶性肿瘤的进展。然而,这种重编程是否有助于NUT癌的发病机制仍然难以捉摸。我们在此报告了一名31岁男性腹膜后出现的NUT癌的尸检病例。值得注意的是,在这个不寻常的NUT癌病例中观察到糖酵解代谢和表观遗传组蛋白修饰的重编程，并且这种现象通过具有含溴结构域4(BRD4)-NUT过表达的体外细胞培养模型得到进一步证实。记录病例的理由是基于我们的发现，揭示代谢和表观遗传重编程可能是NUT癌发病机理的促成因素之一。这可能是开发作为一种新的治疗目标，这种罕见的和积极的癌症类型。
