b'Redefining Research & CareHOW DOES P53 STOP CANCER? An important gene in Wilms tumors ishuman genome. When activated, these p53, the most commonly mutated genesegments, known as retrotransposons, across cancers. can wreak havoc. They have the ability Traditionally, physicians have thoughtto move from one place in the genome that p53 blocks cancer development byto another, causing mutations. These activating a cell suicide program when cellsfindings, based on studying fruit flies and detect mutations or damage in their DNAmice as well as human samples of Wilms instructions. However, a recent study ledand other tumors, help to explain why by cell biologist John Abrams, Ph.D., hascancer genomes are prone to mutations. challenged these assumptions. If validated, the findings will open radically Dr. Abrams team has discoverednew forms of cancer treatment, employingA p53 reporter (green) reveals p53 that p53 prevents the reactivation ofdrugs normally used for viral infections,function associated with mobile element activity during meiosis. Nuclei are blue remnants from viruses integrated in thesuch as HIV. (Wylie et al., Genes Dev, 2016) and cell boundaries are red.Photo Courtesy of Yipin PhotographyFundraising to find a cure for kidney cancer in children Pediatric Kidney Cancer and adolescents. latest treatments and clinical trials.UT Southwestern physicians at ChildrensWilms tumoralso known as nephro- Novel Type of Wilms Tumor IdentifiedHealth provide cutting-edge care for childrenblastomais typically diagnosed inMEET KENNETH CHEN,Kidney Cancer Program investigators with kidney cancers. children ages 3 to 5. It is often not foundM.D., CO-LEADER,have identified a new subtype of Wilms until the cancer has grown quite largetumor. The research team includes Treatment expertise can be vital in treating a(several inches across) and is felt during aPEDIATRICSDrs. Dinesh Rakheja, Kenneth Chen,Discoveries atUT Southwestern rare cancer such as Wilms tumor, diagnosedmedical exam. Treatment requires a teamJoshua Mendell, and James Amatruda.have identified a new Dr. Kenneth Chen, Assistantsubtype of Wilms tumor in fewer than 50 Texas children a year. Manyapproach with specialists from surgery,Professor of Pediatrics, joined theFunded in part by CPRIT (Cancercharacterized by faulty of those children receive treatment andoncology, and radiation oncology. MoreKidney Cancer Program leadershipPrevention and Research Institute ofmiRNA processing. follow-up care from UT Southwestern at thethan 80 percent of children are cured, butin 2019. A physician-scientist, heTexas), the team performed next-gener-Gill Center for Cancer and Blood Disorders,current treatments are associated withdivides his time between his researchation sequencing analyses on 44 WilmsmicroRNAs fine-tune genetic instructionsthat a family of microRNAs called let-7 was at Childrens Health in Dallas. long-term debilitating effects, includ- laboratory and Childrens Medicaltumors from patients at UT Southwestern.that direct the production of particu- missing in tumors with the mutations. As a The Gill Center treats 1 in 5 children ining scarring in the lungs, heart failure,Center Dallas, where he specializesInvestigators discovered several genes thatlar proteins.result, cells produced excessive quantities Texas with cancer. The Center is part of theand increased chances of leukemia.in the treatment and care of childrenwere not previously implicated in the dis- With funding from the SPORE, investi- of proteins that promote cell proliferation. Childrens Oncology Group, funded by theAdditionally, if the cancer recurs, it can bewith cancer and blood disorders. ease. Among them were two, DROSHA andgators are seeking clues to determine howThese efforts are complemented by National Cancer Institute, and offers thedifficult to treat.DICER1, that control the cellular productionmutations in DROSHA and DICER1 affectthose of Dr. Keri Drake, a recipient of a of tiny molecules called microRNAs. Thesecancer development. They have discoveredcareer award from the SPORE. Dr. Drake is evaluating the role of another pathway, the beta-catenin pathway, which is activated in up to 50 percent of Wilms tumors. Ongoing efforts are exploring how the different subtypes respond to therapy, with the goal of developing more tailoredtreatment approaches. (Rakheja, Nat Commun, 2014; Chen et al., GenesDev, 2018) Pediatric oncologist Dr. Jonathan WickiserPhysician-scientist Dr. James Amatruda (far specializes in the care of patients with Wilms tumor.left) partnered with molecular and RNA biologist Dr. Josh Mendell (right) to show how mutations in DROSHA and DICER1 lead to Wilms tumors.56 57'