KMT2A (MLL) fusions in aggressive sarcomas in young adults.
KMT2A (MLL) fusions in aggressive sarcomas in young adults.
复制标题
年轻人侵袭性肉瘤中的 KMT2A (MLL) 融合。
DOI：
10.1111/his.13926
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发表时间：
2019
期刊：
影响因子：
6.4
通讯作者：
Shibata T.
中科院分区：
文献类型：
--
作者：
Yoshida A;Arai Y;Tanzawa Y;Wakai S;Hama N;Kawai A;Shibata T.
目的用组织学和分子生物学相结合的方法鉴定无法分类的肉瘤。方法和结果通过RNA测序，我们在两个病例中鉴定了涉及KMT2A(MLL)的框内融合。病例1为20岁女性，大腿有深部软组织肿块。肿瘤由高度硬化的单形圆形、上皮样和梭形细胞组成，局部CD34、CD31和ERG免疫阳性。病例2是一名30岁的女性，患有肿瘤，影响股骨和周围软组织。肿瘤由BCOR、Wilms瘤1和NKX2-2免疫阳性的单形圆形到梭形细胞组成。这两种肿瘤都是侵袭性的，并已转移到肺部；两名患者都在几年内死亡。RNA测序证实例1为aYAP1(外显子5)-KMT2A(外显子4)融合，例2为Avim(外显子4)-KMT2A(外显子2)融合，均经逆转录聚合酶链式反应、Sanger测序和荧光原位杂交证实。该融合蛋白结构与急性白血病不同，提示了一种新的致癌机制。结论KMT2融合是青年侵袭性不可分类肉瘤的一种亚型。虽然目前还不清楚这些肉瘤是否属于一个单独的组，但KMT2融合作为急性白血病的驱动因素以及最近一篇关于在一个无法分类的肉瘤中识别YAP1-KMT2A的出版物支持了这些融合的重要性。有必要对更多的病例进行进一步的研究，以充分了解KMT2A重排肉瘤的临床病理和分子方面。
AimTo characterise unclassifiable sarcomas by use of a combined histological and molecular approach.Methods and resultsUsing RNA sequencing, we identified in‐frame fusions involvingKMT2A(MLL) in two cases. Case 1 was a 20‐year‐old woman with a deep soft tissue mass in the thigh. The tumour consisted of monomorphic round, epithelioid and spindle cells in a highly sclerotic background that were focally immunopositive for CD34, CD31, and ERG. Case 2 was a 30‐year‐old woman with a tumour that affected the femur and surrounding soft tissue. The tumour consisted of monomorphic round to spindle cells that were immunopositive for BCOR, Wilms tumour 1, and NKX2‐2. Both tumours were aggressive and had metastasised to the lung; both patients died within a few years. RNA sequencing identified aYAP1(exon 5)–KMT2A(exon 4) fusion in case 1 and aVIM(exon 4)–KMT2A(exon 2) fusion in case 2, both of which were confirmed by reverse transcription polymerase chain reaction, Sanger sequencing, and fluorescencein‐situhybridisation. The fusion protein structure was different from that in acute leukaemia, suggesting a novel oncogenic mechanism.ConclusionsKMT2Afusions account for a subset of aggressive unclassifiable sarcomas in young adults. Although it is presently unclear whether these sarcomas belong to a single group, the well‐established role ofKMT2Afusions as drivers of acute leukaemia and a recent publication regarding identification ofYAP1–KMT2Ain one unclassifiable sarcoma support the significance of these fusions. Further studies on additional cases are necessary to fully understand the clinicopathological and molecular aspects ofKMT2A‐rearranged sarcomas.