Neves, JB;
Roberts, K;
Nguyen, JS;
El Sheikh, S;
Tran-Dang, MA;
Horsfield, C;
Mumtaz, F;
... Mitchell, T; + view all
(2022)
Defining the origin, evolution, and immune composition of SDH-deficient renal cell carcinoma.
iScience
, 25
(11)
, Article 105389. 10.1016/j.isci.2022.105389.
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Abstract
Succinate dehydrogenase (SDH)-deficient renal cell carcinoma represents a rare subtype of hereditary kidney cancer. Clinical diagnosis can be challenging and there is little evidence to guide systemic therapeutic options. We performed genomic profiling of a cohort of tumors through the analysis of whole genomes, transcriptomes, as well as flow cytometry and immunohistochemistry in order to gain a deeper understanding of their molecular biology. We find neutral evolution after early tumor activation with a lack of secondary driver events. We show that these tumors have epithelial derivation, possibly from the macula densa, a specialized paracrine cell of the renal juxtaglomerular apparatus. They subsequently develop into immune excluded tumors. We provide transcriptomic and protein expression evidence of a highly specific tumor marker, PAPPA2. These translational findings have implications for the diagnosis and treatment for this rare tumor subtype.
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