Biallelic Alteration and Dysregulation of the Hippo Pathway in Mucinous Tubular and Spindle Cell Carcinoma of the Kidney.
Biallelic Alteration and Dysregulation of the Hippo Pathway in Mucinous Tubular and Spindle Cell Carcinoma of the Kidney.
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DOI：
10.1158/2159-8290.cd-16-0267
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发表时间：
2016-11
期刊：
影响因子：
28.2
通讯作者：
Chinnaiyan AM
中科院分区：
文献类型：
--
作者：
Mehra R;Vats P;Cieslik M;Cao X;Su F;Shukla S;Udager AM;Wang R;Pan J;Kasaian K;Lonigro R;Siddiqui J;Premkumar K;Palapattu G;Weizer A;Hafez KS;Wolf JS Jr;Sangoi AR;Trpkov K;Osunkoya AO;Zhou M;Giannico G;McKenney JK;Dhanasekaran SM;Chinnaiyan AM
黏液性管状梭形细胞癌是一种相对罕见的肾细胞癌亚型，具有独特的形态学和细胞遗传学特征。在这里，我们进行了MTSCC的多机构队列（n=22）的全外显子组和转录组测序。我们证明了在85%的样本中存在Hippo途径肿瘤抑制基因（TSG）的双等位基因缺失和/或Hippo途径基因改变的证据。PTPN 14（31%）和NF 2（22%）是最常见的Hippo通路基因，而其他基因如SAV 1和HIPK 2也以相互排斥的方式参与。在复发性染色体丢失的背景下，突变相当于这些TSG中的双等位基因改变。作为Hippo通路失活的读数，大多数病例（90%）显示出核YAP 1蛋白表达增加。总之，几乎所有的MTSCC病例都表现出Hippo通路失调的证据。
Mucinous tubular and spindle cell carcinoma (MTSCC) is a relatively rare subtype of renal cell carcinoma with distinctive morphologic and cytogenetic features. Here we carry out whole exome and transcriptome sequencing of a multi-institutional cohort of MTSCC (n=22). We demonstrate the presence of either biallelic loss of Hippo pathway tumor suppressor genes (TSGs) and/or evidence of alteration of Hippo pathway genes in 85% of samples. PTPN14 (31%) and NF2 (22%) were the most commonly implicated Hippo pathway genes while other genes such as SAV1 and HIPK2 were also involved in a mutually exclusive fashion. Mutations in the context of recurrent chromosomal losses amounted to bi-allelic alterations in these TSGs. As a read-out of Hippo pathway inactivation, a majority of cases (90%) exhibited increased nuclear YAP1 protein expression. Taken together, nearly all cases of MTSCC exhibit some evidence of Hippo pathway dysregulation.