Somatic Bi-allelic Loss of TSC Genes in Eosinophilic Solid and Cystic Renal Cell Carcinoma.
Somatic Bi-allelic Loss of TSC Genes in Eosinophilic Solid and Cystic Renal Cell Carcinoma.
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嗜酸性固体和囊性肾细胞癌中TSC基因的体细胞双性损失。
DOI：
10.1016/j.eururo.2018.06.007
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发表时间：
2018-10
期刊：
影响因子：
23.4
通讯作者：
Chinnaiyan AM
中科院分区：
文献类型：
--
作者：
Mehra R;Vats P;Cao X;Su F;Lee ND;Lonigro R;Premkumar K;Trpkov K;McKenney JK;Dhanasekaran SM;Chinnaiyan AM
Renal cell carcinomas (RCC) with overlapping histomorphologic features poses diagnostic challenges. This is exemplified in RCCs with eosinophilic cytoplasm that include, eosinophilic, solid and cystic RCC (ESC RCC), RCCs in germline aberrations of tuberous sclerosis complex (TSC) genes mutated (TSC RCC) individuals and other RCC subtypes. Here we used next-generation sequencing (NGS) technology to molecularly profile 7 ESC RCC tumors. Mutational and copy number analysis of NGS data revealed mutually exclusively somatic bi-allelic loss of TSC1 or TSC2 genes both negative regulators of the mammalian target of rapamycin (mTOR) pathway in 85% (6 / 7) of evaluated cases. Thus, lack of germline TSC aberration in matched non-neoplastic renal parenchyma distinguishes ESC RCC from TSC RCC. Immunohistochemistry data shows mTOR pathway activation in all tumors, thus supporting a pathognomonic role for TSC aberrations in ESC RCC. Our study clarifies the molecular identity of ESC RCC, provide basis for the revision of current RCC classification, and may guide future therapeuties. Molecular characterization of ESC RCC revealed recurrent and mutually exclusive somatic homozygous loss of TSC family genes. This observation provides greater insight into the unique biology of this novel type of tumor and potentially expands the therapeutic options for ESC RCC patients.
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影响因子：
23.4
作者：
Moch, Holger;Cubilla, Antonio L.;Ulbright, Thomas M.
通讯作者：
Ulbright, Thomas M.
影响因子：
6.4
作者：
Li Y;Reuter VE;Matoso A;Netto GJ;Epstein JI;Argani P
通讯作者：
Argani P
影响因子：
5.6
作者：
Trpkov, Kiril;Hes, Ondrej;McKenney, Jesse K.
通讯作者：
McKenney, Jesse K.
影响因子：
28.2
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
通讯作者：
Chinnaiyan AM
影响因子：
9.2
作者：
Long, X;Lin, Y;Avruch, J
通讯作者：
Avruch, J