Dissection of tumor and immune heterogeneity of MiT family translocation renal cell carcinomas in mice and human
Final Report Abstract
Translocation renal cell carcinomas (tRCC) are rare but aggressive kidney tumors that primarily affect younger patients. They arise from gene fusions involving parts of the TFE3 or TFEB genes with other genes. Despite their aggressiveness, there are currently no specific treatment options for tRCC. This research project aims to develop and investigate new mouse models for different forms of tRCC. Four models will be compared, each representing a different gene fusion or overexpression: TFEB, TFE3, NONO-TFE3, and ASPSCR1-TFE3. Using these models, we examine how the various genetic alterations affect tumor development, growth, and the composition of the tumor microenvironment. Specifically, we will analyze and compare the kinetics of tumor development, tumor morphology, gene expression profiles, and the composition of immune cell infiltrates in the different models. Additionally, we will correlate the results with data from human tRCC tumors. The insights gained from this study will contribute to a better understanding of the development and progression of tRCC. This could form the basis for developing new, targeted therapeutic approaches. In the long term, we hope to improve treatment options and prognosis for patients with this rare but aggressive cancer type. The project thus has high relevance for patients with tRCC. It could pave the way for personalized therapeutic approaches tailored to the specific genetic alterations of individual tumors. Furthermore, the study provides fundamental insights into the role of gene fusions in cancer development, which could also be relevant for other types of tumors.
Publications
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Racial Disparities in MiT Family Translocation Renal Cell Carcinoma. The Oncologist, 28(11), 1009-1013.
Lu, Xiaofan; Tawanaie, Pour Sedehi Nassim; Su, Xiaoping; Yan, Fangrong; Alhalabi, Omar; Tannir, Nizar M. & Malouf, Gabriel G.
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SMARCB1 regulates a TFCP2L1-MYC transcriptional switch promoting renal medullary carcinoma transformation and ferroptosis resistance. Nature Communications, 14(1).
Vokshi, Bujamin H.; Davidson, Guillaume; Tawanaie, Pour Sedehi Nassim; Helleux, Alexandra; Rippinger, Marc; Haller, Alexandre R.; Gantzer, Justine; Thouvenin, Jonathan; Baltzinger, Philippe; Bouarich, Rachida; Manriquez, Valeria; Zaidi, Sakina; Rao, Priya; Msaouel, Pavlos; Su, Xiaoping; Lang, Hervé; Tricard, Thibault; Lindner, Véronique; Surdez, Didier ... & Malouf, Gabriel G.
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Poster Presentation Title: Oncogenic role of SS18-OCT4 fusion in kidney tumorsCongress: 7e édition des Congrès IFODS (2024) 12.- 14.06.2024 in Paris.
N. Tawanaie Pour Sedehi, B. Vokshi, X. Lu & G. Malouf
