Researchers Shine Light on a Rare Form of Kidney Cancer

Translocation renal cell carcinoma (tRCC) is a rare and aggressive form of kidney cancer. It accounts for about 5 percent of all renal cell carcinomas in adults and about 50 percent in children. Relatively little is known about this cancer subtype, including its molecular underpinnings and the best course of clinical treatment. In a new comprehensive, multicenter study of 152 samples, investigators at Dana-Farber Brigham Cancer Center helped to illuminate the disease’s molecular landscape and clinical features, finding that genetic alterations are rare in tRCC, except for the gene fusion from which it gets its name.  Their work further suggests that tRCCs may be responsive to treatment with immune checkpoint inhibitors.

“We think our findings regarding the potential of immunotherapy combinations could be immediately clinically actionable,” said lead author Ziad El Bakouny, MD, MSc, 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.”

Read more in Cell Reports.

Epigenetic Aging Clock Predicts the Biological Age of Individual Cells

One of the more promising biomarkers to measure biological aging is DNA methylation, an epigenetic modification that alters a specific sequence of DNA nucleotides known as CpG sites. Researchers have traditionally used epigenetic clocks, biochemical tests measuring the levels of DNA methylation, to profile the epigenetic age in bulk tissue samples. Using bulk samples can give an average of the patterns of methylation in tissue but obscures the differences that exist across individual cells. To visualize these patterns in single cells, researchers at the Brigham have developed a technique known as scAge, a statistical program capable of capturing epigenetic age at a single-cell resolution. With scAge, researchers elucidated the mechanisms driving the aging process, attenuation of epigenetic aging, and early embryogenesis-related rejuvenation in murine hepatocytes, muscle, and embryonic stem cells, respectively. Using epigenetic clock approaches, researchers found that individual cell lineages within organisms indeed age and that research on biological aging, at the previously elusive level of the individual cell, is now a possibility.

“Our single-cell approach with scAge may have profound clinical applications for mammalian, somatic, germline, and cancer cells within heterogeneous tissues,” said senior author Vadim N. Gladyshev, PhD, of the Division of Genetics in the Department of Medicine. “Through this paper we wanted to present a framework to profile epigenetic age in single cells, and in the process, found an exciting application at the interface of aging, rejuvenation, and emerging single-cell technologies.”

Read more in Nature Aging.


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