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From the Lab: Scientists Pinpoint Genetic Changes in Radiation-induced Meningiomas

GregoryAuneby Gregory Aune, MD, PhD, CKN Editor


Childhood Cancer Survivors have their own unique set of issues that often go unaddressed by health care professionals once treatment has ended and the child enters adulthood.  Although the last 20 years have seen growth in survivorship research, this research is rarely filtered down to the people who need it most – the survivors and their families.  Dr. Gregory Aune, Pediatric Oncologist, researcher, childhood cancer survivor and advocate, has taken on the position of CKN Editor, Knowledge Translation – Childhood Cancer Survivorship.  His goal is simple:  to help empower childhood cancer survivors to start a dialogue with their doctors by publishing short, easy-to-read research study summaries, like this one.


THE HEADLINE:  Brain Tumor Scientists Map Mutation That Drives Tumors In Childhood Cancer Survivors

THE RESEARCH: Nature Communications:  Therapeutic radiation for childhood cancer drives structural aberrations of NF2 in meningiomas.  Researchers in Canada collected tumor tissue from 31 childhood cancer survivors who developed a secondary radiation-induced meningioma (RIM).  Using the tissue, researchers then completed an extensive array of genomic sequencing analyses and compared the underlying genetic changes of RIM to those that have been reported in sporadic meningiomas (SM, those that occur in the general population and without a history of radiation exposure).  Sequencing analyses completed included whole exome sequencing (genes that encode proteins), detailed analysis of the neurofibromatosis 2 (NF2) gene sequence (known to play a major role in SM biology), RNA sequencing (expressed genes) and methylation profiling (estimation of non-inherited changes in DNA).

KEY FINDINGS:  Like SM, a large fraction (12/31) of RIM had NF2 gene rearrangements.  In contrast, several common mutations that have previously been described in SM were not found in RIM.  These included AKT1, KLF4, TRAF7, and SMO.  16 RIM cases had a loss of chromosome 1p and 22q and overall the chromosomal landscape was more complex than that seen in SM.  Importantly, the patterns of DNA methylation indicated a similar cell of origin for RIM and SM.  

WHAT THIS MEANS FOR CHILDHOOD CANCER SURVIVORS:  Radiation is a critical curative component of treatment for brain tumors and historically leukemia.  Efforts to reduce radiation exposure have resulted in less cranial radiation overall and particularly in leukemia, but there remain a large number of childhood cancer survivors who are at increased risk of developing meningiomas.  (see previous post)  The basic laboratory studies detailed above underscore the importance of ongoing follow-up and surveillance.  As was previously known, survivors are at increased risk of secondary neoplasms. The current research highlights the distinctive biological differences in the tumors that arise in the context of previous treatment exposures such as radiation.  As frequently noted in this blog series, ongoing consistent monitoring by multidisciplinary survivorship clinics is key to maximizing long-term health and quality of life. In addition, survivorparticipation in longitudinal follow-up is also critical to develop research cohorts that can advance our scientific understanding of late health complications.

WHAT THIS MEANS FOR SURVIVORSHIP RESEARCH:  The biological differences found in RIM compared to SM underscores the need to develop research programs and centers that are focused on the molecular and cellular mechanisms that drive late health complications following childhood exposure to chemotherapy and radiation.



Medical Disclaimer:  The information on this site is not intended or implied to be a substitute for professional medical advice, diagnosis or treatment. All content, including text, graphics, images and information, contained on or available through this web site is for general information purposes only.  If you feel the research summarized applies to you or someone you know, talk to your doctor about your concerns.



Videos with Dr. Aune

Presentation on YouTube (Jan 2015):  Eliminating Long-term Health Effects in Cancer Survivors – Gregory Aune, MD, PhD

Interview for the National Coalition for Cancer Survivorship (June 2015):  Hodgkin’s Lymphoma Survivor Dr. Greg Aune Discusses Issues in Long-Term Survivorship Care

Interview with the Washington Post Live Summit (Dec 2016): How cancer lives on in young adults after treatment ends



Dr. Gregory J. Aune is the Stephanie Edlund Distinguished Professor of Pediatric Cancer Research and a St. Baldrick’s Foundation Scholar.  His experience in pediatric cancer spans over 27 years and encompasses his own patient experiences, research in experimental therapeutics, clinical care of pediatric oncology patients, and childhood cancer advocacy.  His interest in pediatric oncology began at age 16, when he was diagnosed with Hodgkin’s lymphoma.  While fortunate to survive, the experiences he encountered as a patient initiated a path towards a research and clinical career aimed at developing less toxic chemotherapy regimens.  His experience as a long-term survivor included open-heart surgery at age 35 to replace his aortic valve and bypass three blocked coronary arteries that were damaged by his teenage cancer therapies.  This life-changing event initiated his research interest in cardiac disease.  His training to become a successful physician scientist and pediatric oncologist has included time spent at some of the most well-respected oncology institutions in the United States including, M.D. Anderson Cancer Center, the National Cancer Institute, and Johns Hopkins Hospital.

Dr. Aune is a national leader in childhood cancer advocacy efforts.  In San Antonio, he has been a leader in local fundraising and awareness efforts.   Since 2010, he has spearheaded efforts by the St. Baldrick’s Foundation and For the Kids Dance Marathon at the University of Texas San Antonio that have raised over $830,000 for childhood cancer patients and research efforts.  In September 2014, his appointment to the National Cancer Institute Council of Research Advocates (NCRA) was announced by NCI Director Dr. Harold Varmus at a White House briefing on childhood cancer.

In addition, Dr. Aune is a policy advisor for the National Coalition for Cancer Survivorship, serves on the Board of Directors of the American Childhood Cancer Organization, is a member of the St. Baldrick’s Foundation National Advocacy Committee, and serves on the scientific advisory board for the Canines-N-Kids foundation.

In May 2015, Dr. Aune addressed the 68th World Health Assembly in Geneva, Switzerland and called on the World Health Organization to make childhood cancer a top global health priority.



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