RNA sequencing of Xp11 translocation-associated cancers reveals novel gene fusions and distinctive clinicopathologic correlations
RNA sequencing of Xp11 translocation-associated cancers reveals novel gene fusions and distinctive clinicopathologic correlations
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Xp11 易位相关癌症的 RNA 测序揭示了新的基因融合和独特的临床病理相关性
DOI：
10.1038/s41379-018-0051-5
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发表时间：
2018-09-01
期刊：
影响因子：
7.5
通讯作者：
Rao, Qiu
中科院分区：
文献类型：
--
作者：
Wang, Xiao-tong;Xia, Qiu-yuan;Rao, Qiu
XP11易位肾细胞癌和相应的间充质肿瘤的特征在于涉及TFE3的多种基因融合。众所周知，具有不同基因融合的肿瘤可能具有不同的临床病理特征。但是，需要对XP11易位相关的癌症进行进一步的深入研究，以探索更有意义的临床病理相关性。总共选择了22例XP11易位相关癌症的情况；通过RNA测序进一步分析了20例病例，以探索其TFE3基因融合伙伴。 RNA测序鉴定了与TFE3相关的基因融合物中的20例（85％）中的17个，包括4个Aspscr1/aspl-TFE3、3 PRCC-TFE3、3 SFPQ/PSF-TFE3、1 nono-TFE3、1 NONO-TFE3、4 Med15-TFE3、1 Med15-TFE3、1 Matr3-TFE3，和1 fubp1-TFE3。通过融合荧光原位杂交（FISH）测定或逆转录酶聚合酶链反应（RT-PCR）验证了结果。通过融合鱼测定法鉴定出具有高度暗示MED15-TFE3肾细胞癌的特定病理特征的2例具有特定病理特征的病例。 We provide the detailed morphologic and immunophenotypic description of the MED15-TFE3 renal cell carcinomas, which frequently demonstrate extensively cystic architecture, similar to multilocular cystic renal neoplasm of low malignant potential, and expressed cathepsin K and melanotic biomarker Melan A. This is the first time to correlate the MED15-TFE3 renal cell carcinoma with specific临床病理特征。我们还报告了与Med15-TFE3基因融合的相应间充质肿瘤的第一个情况。鉴定了其他新型的TFE3基因融合伙伴MATR3和FUBP1。 Cases with ASPSCR1-TFE3, SFPQ-TFE3, PRCC-TFE3, and NONO-TFE3 gene fusion showed a wide variability in morphologic features, including invasive tubulopapillary pattern simulating collecting duct carcinoma, extensive calcification and ossification, and overlapping and high columnar cells with nuclear grooves mimicking tall cell variant of papillary thyroid carcinoma.此外，我们分别评估了TFE3免疫组织化学，TFE3 FISH，RT-PCR和RNA测序的能力，从而亚分类XP11易位相关癌症。总而言之，我们的研究扩大了TFE3基因融合伙伴列表以及XP11易位相关癌症的临床病理特征，并突出了将XP11易位相关的癌症结合起来，结合形态，免疫组织化学和多分子技术的XP11易位相关癌症的重要性。
Both Xp11 translocation renal cell carcinomas and the corresponding mesenchymal neoplasms are characterized by a variety of gene fusions involving TFE3. It has been known that tumors with different gene fusions may have different clinicopathologic features; however, further in-depth investigations of subtyping Xp11 translocation-associated cancers are needed in order to explore more meaningful clinicopathologic correlations. A total of 22 unusual cases of Xp11 translocation-associated cancers were selected for the current study; 20 cases were further analyzed by RNA sequencing to explore their TFE3 gene fusion partners. RNA sequencing identified 17 of 20 cases (85%) with TFE3-associated gene fusions, including 4 ASPSCR1/ASPL-TFE3, 3 PRCC-TFE3, 3 SFPQ/PSF-TFE3, 1 NONO-TFE3, 4 MED15-TFE3, 1 MATR3-TFE3, and 1 FUBP1-TFE3. The results have been verified by fusion fluorescence in situ hybridization (FISH) assays or reverse transcriptase polymerase chain reaction (RT-PCR). The remaining 2 cases with specific pathologic features highly suggestive of MED15-TFE3 renal cell carcinoma were identified by fusion FISH assay. We provide the detailed morphologic and immunophenotypic description of the MED15-TFE3 renal cell carcinomas, which frequently demonstrate extensively cystic architecture, similar to multilocular cystic renal neoplasm of low malignant potential, and expressed cathepsin K and melanotic biomarker Melan A. This is the first time to correlate the MED15-TFE3 renal cell carcinoma with specific clinicopathologic features. We also report the first case of the corresponding mesenchymal neoplasm with MED15-TFE3 gene fusion. Additional novel TFE3 gene fusion partners, MATR3 and FUBP1, were identified. Cases with ASPSCR1-TFE3, SFPQ-TFE3, PRCC-TFE3, and NONO-TFE3 gene fusion showed a wide variability in morphologic features, including invasive tubulopapillary pattern simulating collecting duct carcinoma, extensive calcification and ossification, and overlapping and high columnar cells with nuclear grooves mimicking tall cell variant of papillary thyroid carcinoma. Furthermore, we respectively evaluated the ability of TFE3 immunohistochemistry, TFE3 FISH, RT-PCR, and RNA sequencing to subclassify Xp11 translocation-associated cancers. In summary, our study expands the list of TFE3 gene fusion partners and the clinicopathologic features of Xp11 translocation-associated cancers, and highlights the importance of subtyping Xp11 translocation-associated cancers combining morphology, immunohistochemistry, and multiple molecular techniques.