PDF(Pubmed)
Abstract：
NUT midline carcinoma is a rare malignancy most commonly seen in adolescents and young adults. The disease presents most often in the lung or head and neck area but can be seen occasionally elsewhere. The diagnosis can be difficult and requires a high degree of suspicion with demonstration of the classic fusion rearrangement mutation of the NUTM1 gene with one of a variety of partners by immunohistochemistry, fluorescent in situ hybridization, or genomic analysis. Survival is usually only a number of months with few long-term survivors. Here we report one of the longest-known survivors of this disease treated with surgery and radiation without additional therapy. Systemic treatment approaches including the use of chemotherapy and BET and histone deacetylase inhibitors have yielded modest results. Further studies of these, as well as p300 and CDK9 inhibitors and combinations of BET inhibitors with chemotherapy or CDK 4/6 inhibitors, are being evaluated. Recent reports suggest there may be a role for immune checkpoint inhibitors, even in the absence of high tumor mutation burden or PD-L1 positivity. RNA sequencing of this patient\'s tumor demonstrated overexpression of multiple potentially targetable genes. Given the altered transcription that results from the causative mutation multi-omic evaluation of these tumors may uncover druggable targets for treatment.
摘要：
NUT中线癌是一种罕见的恶性肿瘤，最常见于青少年和年轻人。该疾病最常见于肺部或头颈部，但偶尔在其他地方可见。诊断可能很困难，需要高度怀疑，通过免疫组织化学证明NUTM1基因与多种伴侣之一的经典融合重排突变，荧光原位杂交,或基因组分析。生存通常只有几个月，很少有长期幸存者。在这里，我们报告了该疾病已知时间最长的幸存者之一，该患者接受了手术和放射治疗，而无需额外治疗。包括使用化学疗法和BET和组蛋白脱乙酰酶抑制剂的全身治疗方法已经产生了适度的结果。对这些的进一步研究，以及p300和CDK9抑制剂以及BET抑制剂与化疗或CDK4/6抑制剂的组合，正在评估。最近的报道表明，免疫检查点抑制剂可能有作用，即使在没有高肿瘤突变负担或PD-L1阳性的情况下。该患者肿瘤的RNA测序显示了多种潜在靶向基因的过表达。鉴于由致病突变导致的转录改变，对这些肿瘤的多组评估可能会发现可用于治疗的药物靶标。
