Neuro-Oncology

Research

Dr. Robert Wechsler-Reya talks about his work with RCIGM.

In 2016, the Institute established the Joseph Clayes III Research Center for Neuro-Oncology and Genomics. This was made possible by a generous $10 million endowment from the Joseph Clayes III Charitable Trust. The Center aims to accelerate the translation of leading-edge genomic research into prevention, diagnosis, treatment and cures.

The endowment of the Joseph Clayes III Charitable Trust led to the formation of the Molecular Tumor Board at Rady Children’s Hospital- San Diego in 2017, which consists of physician scientists, clinicians and researchers in the field of tumor genetics. The board recommends advanced testing, including rapid whole genome sequencing and functional drug screening, for some children with tumors in the brain or spinal cord. The members of the tumor board study the results of these tests and try to detect novel mutations and pathways involved in tumor growth.

Thanks to funding from the Joseph Clayes III Charitable Trust, Dr. Chavez, and his colleagues have analyzed the molecular structures of tumors in nearly 70 patients. The team is motivated by the idea that soon, they will be able to not only provide precision diagnostics, but also more informed treatment recommendations. Instead of relying on educated guesses, they aim to offer families a clearer understanding of their child’s tumor and more targeted treatment options.

megan_paul_md_square

Megan Paul, MD

PI, and Clinical Co-lead of the International Review Board-approved pediatric neuro-oncology MTB

Dr. Megan Paul, a pediatric neuro-oncologist, serves as the clinical director and principal investigator of the Molecular Tumor Board. She has been involved with the project since 2018, during her fellowship training. The project is a pioneering attempt at personalized medicine for children with rare brain tumors, made possible by recent technological and scientific advances that allow for increasingly precise tumor characterization. In recent years, there has also been a significant increase in understanding the molecular differences between tumors. The Molecular Tumor Board is leveraging this information by investigating the DNA, RNA, and epigenome of each patient’s tumor, enabling more accurate diagnoses based on highly detailed tumor characterizations. Doctor Profile 

dr_lukas_chavez_square

Lukas Chavez, PhD

Scientific Director Pediatric Neuro-Oncology Molecular Tumor Board; Associate Professor Cancer Genome & Epigenetics Program Sanford Burnham Prebys (SBP) Medical Discovery Institute; Associate Adjunct Professor, Department of Medicine, UC San Diego.

Dr. Lukas Chavez, a pediatric brain tumor researcher and Scientific Director of the Molecular Tumor Board, focuses on understanding the genetic causes of pediatric brain tumor development and progression. Chavez’s lab aims to identify new therapeutic interventions by testing chemical compounds and conducting genetic inhibition experiments on tumor models derived from patient biopsies. These models are used to explore personalized treatments for rare tumors that currently lack established therapies.  Lukas Chavez Lab 

dr_raju

Praveen Raju, MD., PhD

Pediatric Neuro-Oncology Director & Nathan Gordon Chair in Neuro-Oncology

Dr. Praveen Raju, MD, PhD, joins Rady Children’s to lead the Neuro-Oncology Program, bringing expertise on advancing research and treatment for pediatric brain and spinal tumors, including medulloblastoma. His work emphasizes addressing different molecular subtypes and developing innovative therapies that are both effective and safer for children. Press Release | Doctor Profile

Related Study

Publications​

Parent and patient knowledge and attitudes about cancer predisposition syndrome genetic testing in pediatric oncology: Understanding sociodemographic and parent-child differences

  • Rapoport CS, Masser-Frye D, Mehta S, Choi AK, Olfus S, Korhummel M, Hoyo V, Dimmock D, Malcarne VL, Kuo DJ. Parent and patient knowledge and attitudes about cancer predisposition syndrome genetic testing in pediatric oncology: Understanding sociodemographic and parent-child differences. Cancer Rep (Hoboken). 2024 Sep;7(9):e2119.

Cancer Rep (Hoboken). 2024 Sep;7(9):e2119. doi: 10.1002/cnr2.2119.

ABSTRACT

BACKGROUND: Cancer predisposition syndromes (CPS) impact about 10% of patients with pediatric cancer. Genetic testing (CPS-GT) has multiple benefits, but few studies have described parent and child knowledge and attitudes regarding CPS-GT decision-making. This study examined parent and patient CPS-GT decision-making knowledge and attitudes.

PROCEDURE: English- or Spanish-speaking parents of children with pediatric cancer and patients with pediatric cancer ages 15-18 within 12 months of diagnosis or relapse were eligible to participate. Seventy-five parents and 19 parent-patient dyads (N = 94 parents, 77.7% female, 43.6% Latino/a/Hispanic; 19 patients, 31.6% female) completed surveys measuring CPS-GT-related beliefs. Independent samples t-tests compared parent responses across sociodemographic characteristics and parent-patient responses within dyads.

RESULTS: Spanish-speaking parents were significantly more likely than English-speaking parents to believe that CPS-GT not being helpful (p < .001) and possibly causing personal distress (p = .002) were important considerations for deciding whether to obtain CPS-GT. Parents with less than four-year university education, income less than $75,000, or Medicaid (vs. private insurance) were significantly more likely to endorse that CPS-GT not being helpful was an important consideration for deciding whether to obtain CPS-GT (p < .001). Parents felt more strongly than patients that they understood what CPS-GT was (p = .01) and that parents should decide whether patients under 18 should receive CPS-GT (p = .002).

CONCLUSIONS: Spanish-speaking parents and parents with lower socioeconomic statuses were more strongly influenced by the potential disadvantages of CPS-GT in CPS-GT decision-making. Parents felt more strongly than patients that parents should make CPS-GT decisions. Future studies should investigate mechanisms behind these differences and how to best support CPS-GT knowledge and decision-making.

PMID:39233650 | DOI:10.1002/cnr2.2119

Circular extrachromosomal DNA promotes tumor heterogeneity in high-risk medulloblastoma

  • Chapman OS, Luebeck J, Sridhar S, Wong IT, Dixit D, Wang S, Prasad G, Rajkumar U, Pagadala MS, Larson JD, He BJ, Hung KL, Lange JT, Dehkordi SR, Chandran S, Adam M, Morgan L, Wani S, Tiwari A, Guccione C, Lin Y, Dutta A, Lo YY, Juarez E, Robinson JT, Korshunov A, Michaels JA, Cho YJ, Malicki DM, Coufal NG, Levy ML, Hobbs C, Scheuermann RH, Crawford JR, Pomeroy SL, Rich JN, Zhang X, Chang HY, Dixon JR, Bagchi A, Deshpande AJ, Carter H, Fraenkel E, Mischel PS, Wechsler-Reya RJ, Bafna V, Mesirov JP, Chavez L.

Nat Genet. 2023 Nov 9. doi: 10.1038/s41588-023-01551-3. Online ahead of print.

ABSTRACT

Circular extrachromosomal DNA (ecDNA) in patient tumors is an important driver of oncogenic gene expression, evolution of drug resistance and poor patient outcomes. Applying computational methods for the detection and reconstruction of ecDNA across a retrospective cohort of 481 medulloblastoma tumors from 465 patients, we identify circular ecDNA in 82 patients (18%). Patients with ecDNA-positive medulloblastoma were more than twice as likely to relapse and three times as likely to die within 5 years of diagnosis. A subset of tumors harbored multiple ecDNA lineages, each containing distinct amplified oncogenes. Multimodal sequencing, imaging and CRISPR inhibition experiments in medulloblastoma models reveal intratumoral heterogeneity of ecDNA copy number per cell and frequent putative ‘enhancer rewiring’ events on ecDNA. This study reveals the frequency and diversity of ecDNA in medulloblastoma, stratified into molecular subgroups, and suggests copy number heterogeneity and enhancer rewiring as oncogenic features of ecDNA.

PMID:37945900 | DOI:10.1038/s41588-023-01551-3

The genomic landscape of familial glioma

  • Choi DJ, Armstrong G, Lozzi B, Vijayaraghavan P, Plon SE, Wong TC, Boerwinkle E, Muzny DM, Chen HC, Gibbs RA, Ostrom QT, Melin B, Deneen B, Bondy ML; Gliogene Consortium; Genomics England Research Consortium; Bainbridge MN, Amos CI, Barnholtz-Sloan JS, Bernstein JL, Claus EB, Houlston RS, Il'yasova D, Jenkins RB, Johansen C, Lachance D, Lai R, Melin BS, Merrell RT, Olson SH, Sadetzki S, Schildkraut J, Shete S, Ambrose JC, Arumugam P, Bevers R, Bleda M, Boardman-Pretty F, Boustred CR, Brittain H, Brown MA, Caulfield MJ, Chan GC, Giess A, Griffin JN, Hamblin A, Henderson S, Hubbard TJP, Jackson R, Jones LJ, Kasperaviciute D, Kayikci M, Kousathanas A, Lahnstein L, Lakey A, Leigh SEA, Leong IUS, Lopez FJ, Maleady-Crowe F, McEntagart M, Minneci F, Mitchell J, Moutsianas L, Mueller M, Murugaesu N, Need AC, O'Donovan P, Odhams CA, Patch C, Perez-Gil D, Pereira MB, Pullinger J, Rahim T, Rendon A, Rogers T, Savage K, Sawant K, Scott RH, Siddiq A, Sieghart A, Smith SC, Sosinsky A, Stuckey A, Tanguy M, Taylor Tavares AL, Thomas ERA, Thompson SR, Tucci A, Welland MJ, Williams E, Witkowska K, Wood SM, Zarowiecki M.

Sci Adv. 2023 Apr 28;9(17):eade2675. doi: 10.1126/sciadv.ade2675. Epub 2023 Apr 28.

ABSTRACT

Glioma is a rare brain tumor with a poor prognosis. Familial glioma is a subset of glioma with a strong genetic predisposition that accounts for approximately 5% of glioma cases. We performed whole-genome sequencing on an exploratory cohort of 203 individuals from 189 families with a history of familial glioma and an additional validation cohort of 122 individuals from 115 families. We found significant enrichment of rare deleterious variants of seven genes in both cohorts, and the most significantly enriched gene was HERC2 (P = 0.0006). Furthermore, we identified rare noncoding variants in both cohorts that were predicted to affect transcription factor binding sites or cause cryptic splicing. Last, we selected a subset of discovered genes for validation by CRISPR knockdown screening and found that DMBT1, HP1BP3, and ZCH7B3 have profound impacts on proliferation. This study performs comprehensive surveillance of the genomic landscape of familial glioma.

PMID:37115922 DOI:10.1126/sciadv.ade2675

View More Publications

News

View All News

Want to Learn More?

View Our Publications

Partner With Us

Order a Test

About Us

STAY UP TO DATE

© 2025 Rady Children's Institute for Genomic Medicine.

Follow Us
Icon-linkedin Twitter

Contact Us About BeginNGS