Details

Autor(en) / Beteiligte

• Mehra, Rohit
• Vats, Pankaj
• Cao, Xuhong
• Su, Fengyun
• Lee, Nicole D.
• Lonigro, Robert
• Premkumar, Kumpati
• Trpkov, Kiril
• McKenney, Jesse K.
• Dhanasekaran, Saravana M.
• Chinnaiyan, Arul M.

Titel

Somatic Bi-allelic Loss of TSC Genes in Eosinophilic Solid and Cystic Renal Cell Carcinoma

Ist Teil von

• European urology, 2018-10, Vol.74 (4), p.483-486

Ort / Verlag

Switzerland: Elsevier B.V

Erscheinungsjahr

2018

Link zum Volltext

Quelle

ScienceDirect Journals (5 years ago - present)

Beschreibungen/Notizen

• 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. We used next-generation sequencing (NGS) technology to molecularly profile seven 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, provides basis for the revision of current RCC classification, and may guide future therapeutic strategies. Molecular characterization of eosinophilic solid and cystic renal cell carcinomas (ESC RCC) revealed recurrent and mutually exclusive somatic homozygous loss of tuberous sclerosis complex 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. Next generation sequencing characterization of eosinophilic solid and cystic renal cell carcinoma revealed mutually exclusive, somatic, bi-allelic loss of either TSC1 or TSC2, a pattern distinct from the morphologically similar tuberous sclerosis complex renal cell carcinoma, in which the Knudson's two-hit in tumor suppressor genes always includes a germline component.