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Researchers Reveal Underlying Mechanisms of Rare Form of Kidney Cancer

Translocation renal cell carcinoma (tRCC) is a rare and aggressive form of kidney cancer. It was recognized as a type of kidney cancer in 2004 and accounts for about 5% of all renal cell carcinomas in adults and about 50% in children, yet the underlying mechanisms are not fully understood. Now, researchers at Dana-Farber Brigham Cancer Center have helped shine a light on the disease’s molecular landscape and clinical features.

The researchers discovered genetic alterations are rare in tRCC, except for the gene fusion from which it gets its name. Their findings suggest that tRCC may be responsive to treatment with immune checkpoint inhibitors.

Their research is published in the journal Cell Reports in an article titled, “Integrative clinical and molecular characterization of translocation renal cell carcinoma.”

“tRCC is a poorly characterized subtype of kidney cancer driven by MiT/TFE gene fusions,” the researchers wrote. “Here, we define the landmarks of tRCC through an integrative analysis of 152 patients with tRCC identified across genomic, clinical trial, and retrospective cohorts. Most tRCCs harbor few somatic alterations apart from MiT/TFE fusions and homozygous deletions at chromosome 9p21.3 (19.2% of cases).”

“An intriguing feature of tRCC is that it can exhibit diverse histologic features that may mimic almost all other subtypes of RCC,” noted the researchers.

The researchers leveraged the “histologic overlap” between tRCC and other RCC subtypes to identify tRCC cases from across multiple genomic, clinical trial, and retrospective datasets. They combined cases with the profiling of prospectively identified patients with tRCC to comprehensively characterize the molecular landscape, clinical features, and treatment outcomes for this disease.

“Altogether, we demonstrate the power of an integrative clinico-genomic analysis to illuminate the molecular underpinnings and clinical features of tRCC,” the researchers wrote. “Our work inspires multiple hypotheses that can be pursued in future studies to further dissect the biology of this rare cancer. These data also lay the framework for the development and testing of mechanism-driven therapeutic regimens in tRCC.”

“We think our findings regarding the potential of immunotherapy combinations could be immediately clinically actionable,” said lead author Ziad El Bakouny, MD, a resident in internal medicine at the Brigham. “Because this cancer is so rare, it is difficult to have clinical trials dedicated to it. Comprehensively studying its molecular and clinical features may help us develop a better roadmap for treatment.”

The post Researchers Reveal Underlying Mechanisms of Rare Form of Kidney Cancer appeared first on GEN – Genetic Engineering and Biotechnology News.

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