Diolaiti Daniel, Dela Cruz Filemon S, Gundem Gunes, Bouvier Nancy, Boulad Mathieu, Zhang Yanming, Chou Alexander J, Dunkel Ira J, Sanghvi Rashesh, Shah Minita, Geiger Heather, Rahman Sadia, Felice Vanessa, Wrzeszczynski Kazimierz O, Darnell Robert B, Antonescu Cristina R, French Christopher A, Papaemmanuil Elli, Kung Andrew L, Shukla Neerav
Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
Cold Spring Harb Mol Case Stud. 2018 Dec 17;4(6). doi: 10.1101/mcs.a003194. Print 2018 Dec.
-rearranged tumors are defined by the presence of a gene fusion between and various gene partners and typically follow a clinically aggressive disease course with poor outcomes despite conventional multimodality therapy. -rearranged tumors display histologic features of a poorly differentiated carcinoma with areas of focal squamous differentiation and typically express the fusion gene defining a distinct clinicopathologic entity-NUT carcinoma (NC). NCs with mesenchymal differentiation have rarely been described in the literature. In this report, we describe the characterization of two cases of high-grade spindle cell sarcoma harboring a novel fusion. Whole-genome sequencing identified the presence of complex rearrangements resulting in a fusion gene in the absence of other significant somatic mutations. Genetic rearrangement was confirmed by fluorescence in situ hybridization, and expression of the fusion gene product was confirmed by transcriptomic analysis. The fusion protein was predicted to retain nearly the entire protein sequence of both MGA (exons 1-22) and NUTM1 (exons 3-8). Histopathologically, both cases were high-grade spindle cell sarcomas without specific differentiation markers. In contrast to typical cases of NC, these cases were successfully treated with aggressive local control measures (surgery and radiation) and both patients remain alive without disease. These cases describe a new subtype of -rearranged tumors warranting expansion of diagnostic testing to evaluate for the presence of or alternative gene fusions in the diagnostic workup of high-grade spindle cell sarcomas or small round blue cell tumors of ambiguous lineage.
-重排肿瘤是由与各种基因伙伴之间的基因融合所定义，尽管采用传统的多模式治疗，其通常遵循临床侵袭性疾病进程且预后较差。-重排肿瘤表现出低分化癌的组织学特征，伴有局灶性鳞状分化区域，并且通常表达定义一种独特临床病理实体——NUT癌（NC）的融合基因。文献中很少描述具有间充质分化的NC。在本报告中，我们描述了两例携带新型融合的高级别梭形细胞肉瘤的特征。全基因组测序确定存在复杂重排，导致在没有其他显著体细胞突变的情况下出现融合基因。通过荧光原位杂交证实了基因重排，通过转录组分析证实了融合基因产物的表达。预测融合蛋白保留了MGA（外显子1 - 22）和NUTM1（外显子3 - 8）几乎整个蛋白质序列。组织病理学上，两例均为高级别梭形细胞肉瘤，无特异性分化标志物。与典型的NC病例不同，这些病例通过积极的局部控制措施（手术和放疗）成功治疗，两名患者均存活且无疾病。这些病例描述了一种新的 -重排肿瘤亚型，有必要扩大诊断检测，以评估在高级别梭形细胞肉瘤或谱系不明确的小圆蓝细胞肿瘤的诊断工作中是否存在或替代融合基因。
