Genomics Facility, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA.
Department of Pathology, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA.
Mod Pathol. 2019 May;32(5):710-716. doi: 10.1038/s41379-018-0191-7. Epub 2019 Jan 8.
Microphthalmia-associated transcription factor (MiT) family translocation renal cell carcinoma harbors variable gene fusions involving either TFE3 or TFEB genes. Multiple 5' fusion partners for TFE3 have been reported, including ASPSCR1, CLTC, DVL2, LUC7L3, KHSRP, PRCC, PARP14, NONO, SFPQ1, MED15, and RBM10. Each of these fusion genes activates TFE3 transcription which can be detected by immunostaining. Using targeted RNA-sequencing, TFE3 fusion gene partners were identified in 5 cases of TFE3 immunohistochemistry positive translocation renal cell carcinoma. Three cases demonstrated known fusions: ASPSCR1-TFE3, MED15-TFE3 and RBM10-TFE3. However, two cases showed unreported NEAT1-TFE3 and KAT6A-TFE3 fusion transcripts. The NEAT1-TFE3 RCC arose in a 59-year-old male; which demonstrated overlapping morphological features seen in NEAT2(MALAT1)-TFEB t(6;11) renal cell carcinoma, including biphasic alveolar/nested tumor cells with eosinophilic cytoplasm. The KAT6A-TFE3 renal cell carcinoma demonstrated typical morphological features of TFE3/Xp11 renal cell carcinoma including papillae, eosinophilic cytoplasm with focal clearing and abundant psammoma bodies. KAT6A gene fusion was reported in some cases of acute myeloid leukemia, which has not been previously reported in solid tumors. This report highlights the genetic complexity of TFE3 translocation renal cell carcinoma; and RNA-sequencing is a powerful approach for elucidating the underlying genetic alterations.
小眼畸形相关转录因子（MiT）家族易位性肾细胞癌具有涉及 TFE3 或 TFEB 基因的可变基因融合。已经报道了 TFE3 的多个 5'融合伙伴，包括 ASPSCR1、CLTC、DVL2、LUC7L3、KHSRP、PRCC、PARP14、NONO、SFPQ1、MED15 和 RBM10。这些融合基因中的每一个都激活了 TFE3 转录，这可以通过免疫染色来检测。使用靶向 RNA 测序，在 5 例 TFE3 免疫组化阳性易位性肾细胞癌中鉴定了 TFE3 融合基因伙伴。3 例显示已知融合：ASPSCR1-TFE3、MED15-TFE3 和 RBM10-TFE3。然而，有 2 例显示了未报道的 NEAT1-TFE3 和 KAT6A-TFE3 融合转录本。NEAT1-TFE3 RCC 发生在 59 岁男性；表现出与 NEAT2(MALAT1)-TFEB t(6;11)肾细胞癌重叠的形态特征，包括双相肺泡/巢状肿瘤细胞，具有嗜酸性细胞质。KAT6A-TFE3 肾细胞癌表现出 TFE3/Xp11 肾细胞癌的典型形态特征，包括乳头、嗜酸性细胞质伴局灶性透明变性和丰富的砂粒体。KAT6A 基因融合在一些急性髓细胞白血病病例中被报道，在实体肿瘤中尚未被报道。本报告强调了 TFE3 易位性肾细胞癌的遗传复杂性；RNA 测序是阐明潜在遗传改变的有力方法。
