Identification of a novel PARP14-TFE3 gene fusion from 10-year-old FFPE tissue by RNA-seq
Identification of a novel PARP14-TFE3 gene fusion from 10-year-old FFPE tissue by RNA-seq
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DOI：
10.1002/gcc.22261
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发表时间：
2015-08-01
影响因子：
3.7
通讯作者：
Zhong, Minghao
中科院分区：
文献类型：
--
作者：
Huang, Weihua;Goldfischer, Michael;Zhong, Minghao
Xp 11（TFE 3）易位肾细胞癌（RCC）在2004年WHO分类中被正式确认为RCC的一个独特亚型。这种肿瘤的特点是几个染色体易位之间的TFE 3-涉及Xp11.2断点和各种融合伙伴。到目前为止，已经确定了5个伴侣基因，即1 q21中的PRCC，1 q34中的PSF，17 q25中的ASPL，17 q23中的CLTC和Xq 12中的NONO;并且已经报道了另外3个未定义伴侣基因的易位：t（X;3）（p11;q23），t（X;10）（p11;q23）和t（X;19）（p11;q13）。在这里，我们报告了一种新的TFE 3融合伴侣，PARP 14在染色体band 3q 21的鉴定。我们在一个10岁的FFPE（福尔马林固定，石蜡包埋）组织样本上使用了RNA-seq，该样本携带了在原始细胞遗传学研究中检测到的t（X;3）（p11;q23）。RT-PCR和桑格测序证实，融合基因将PARP 14前两个外显子的5 '端与TFE 3的5个外显子的3'端连接起来。与先前报道的其他TFE 3融合类似，预测的PARP 14-TFE 3产物保留了TFE 3的核定位和DNA结合结构域。这一发现扩展了TFE 3易位伴侣基因的列表，并再次强调了TFE 3融合蛋白在该肿瘤中的重要致癌作用。我们的结果也清楚地证明了在临床FFPE中通过RNA-seq鉴定染色体易位的可行性，这些染色体易位易于获得并且与有价值的临床信息相关。(c)2015 Wiley Periodicals，Inc.
Xp11 (TFE3) translocation renal cell carcinoma (RCC) is officially recognized as a distinct subtype of RCC in the 2004 WHO classification. This neoplasm is characterized by several chromosomal translocations between the TFE3-involving Xp11.2 breakpoint and various fusion partners. To date, five partner genes have been identified, that is, PRCC in 1q21, PSF in 1q34, ASPL in 17q25, CLTC in 17q23, and NONO in Xq12; and three additional translocations have been reported with no partner gene being defined: t(X;3)(p11;q23), t(X;10)(p11;q23), and t(X;19)(p11;q13). Here, we report the identification of a novel TFE3 fusion partner, PARP14 in chromosome band3q21. We used RNA-seq on a 10-year-old FFPE (formalin-fixed, paraffin-embedded) tissue sample, which carried t(X;3)(p11;q23) as detected in the original cytogenetic study. The fusion transcript connected the 5'-end of the first two exons of PARP14 to the 3'-end of five exons of TFE3, which was verified by reverse transcription PCR (RT-PCR) and Sanger sequencing. Similar to other TFE3 fusions previously reported, the predicted PARP14-TFE3 product retains the nuclear localization and DNA-binding domains of TFE3. This finding expands the list of TFE3 translocation partner genes and re-emphasizes the essential oncogenic role of TFE3 fusion proteins in this tumor. Our result also clearly demonstrated the feasibility of identifying chromosomal translocation by RNA-seq in clinical FFPE, which are easily accessible and associated with valuable clinical information. (c) 2015 Wiley Periodicals, Inc.