David Malkin

Administrative Assistant
Arlene Zaldivar
T: 416-813-7753
E: arlene.zaldivar@sickkids.ca
 

At a Glance

• Li-Fraumeni syndrome/p53Precision Medicine
• Cancer genetics & genomics Cancer predisposition
• Sarcomas and Adrenocortical Cancers

Short Bio

Dr. Malkin received his medical degree from the University of Toronto in 1984 and completed his residency in paediatrics and paediatric hematology/oncology at The Hospital for Sick Children in Toronto. He completed post-doctoral research training in molecular genetics at Massachusetts General Hospital, Harvard University, where he discovered the link between germline mutations in the TP53 tumor suppressor gene and the Li-Fraumeni cancer susceptibility syndrome. Dr. Malkin returned to Canada to accept a faculty position at SickKids and University of Toronto in 1992.

Dr. Malkin is Professor of Pediatrics and Medical Biophysics in the Temerty Faculty of Medicine, University of Toronto. He holds the CIBC Children’s Foundation Chair in Child Health Research, is a Senior Staff Oncologist in the Division of Hematology/Oncology, Director of the Cancer Genetics program, and a Senior Scientist in the Genetics and Genome Biology Program at The Hospital for Sick Children in Toronto. Dr. Malkin is the Lead of the SickKids Precision Child Health initiative. He is co-Director of the SickKids Cancer Sequencing (KiCS) program which integrates and translates next generation sequencing into clinical care of children with cancer, and Director of the pan-Canadian multi-institutional PRecision Oncology For Young peopLE (PROFYLE) initiative which is establishing a pipeline to incorporate next generation sequencing into novel clinical trials (‘precision oncology’) for children and young adults with hard-to-treat cancers across Canada. Dr. Malkin’s research program focuses on genetic and genomic mechanisms of childhood cancer susceptibility which he has explored particularly in the context of TP53 and Li-Fraumeni syndrome. Recently, his work has addressed the application of genomics to develop rational clinical surveillance and treatment guidelines for children and adults at genetic ‘high risk’ for cancer. He has published over 250 peer-reviewed articles and has received several awards recognizing his dedication to clinical care, advocacy, research, medical education and mentorship. His research has been funded by the Terry Fox Research Institute, Canadian Cancer Society, Canadian Institutes for Health Research, Canada Foundation for Innovation, Genome Canada, the National Institutes of Health (US) and the Department of Defense (US).

Research Synopsis

Dr. Malkin's research is closely integrated with his clinical field of expertise. Specifically, his research program focuses primarily on genetic mechanisms of childhood cancer susceptibility and the genetic basis of childhood sarcomas (cancers of bone, muscle and other soft tissues). His research team was the first to demonstrate that highly variable regions of DNA, termed copy number variations, are found in excess in the blood of individuals who harbor germline TP53 mutations, both children and adults, at very high risk of developing cancer and may represent the earliest genetic changes that ultimately lead to development of cancer.

In addition, in collaboration with several national and international colleagues, he is studying the genome of children with specific types of brain tumors and sarcomas, using high-resolution genomic platforms, to identify novel genetic biomarkers of disease susceptibility and outcome. Recently, his work has focused on application of this genetic/genomic information to develop rational clinical surveillance and treatment guidelines for children and adults deemed at genetic ‘high risk’ for cancer. In his work on the common pediatric soft tissue tumor, rhabdomyosarcoma, Dr. Malkin has studied the molecular and cell biology pathways that are associated with the development and progression of these cancers, and has identified molecules that might represent viable targets for novel drug therapies.

Dr. Malkin’s research program focuses on understanding the genetic and genomic mechanisms of childhood cancer susceptibility. Recently, his work has addressed the application of genomics to develop rational clinical surveillance and treatment guidelines for children and adults at genetic “high risk” for cancer. Specific research areas include:

• Development of innovative clinical and molecular biomarker (circulating tumor DNA) approaches for early cancer detection in carriers of germline TP53 mutations (Li-Fraumeni syndrome (LFS)).
• Exploration and implementation of pharmacologic interventions to inhibit tumor formation in Trp53-mutant animal models and human TP53 mutation carriers.
• Identification of (epi) genomic events that modify tumor age of onset and phenotype in TP53 mutation carriers.
• Implementation of precision oncology platforms, integrating next generation sequencing with novel clinical trial design, for children with difficult-to-treat cancer.

Recent Publications

1. Anderson ND, de Borja R, Young M, Fuligni F, Rosic A, Roberts ND, Hajjar S, Novokmet A, Kowalski PE, Anaka M, Davidson S, Zarrei M, Id Said B, Schreiner LC, Marchand R, Sitter J, Gogkoz N, Brunga L, Graham GT, Fullam A, Pillay N, Toretsky JA, Yoshida A, Shibata T, Metzler M, Somers GR, Scherer SW, Flanagan AM, Campbell PJ, Schiffman J, Shago M, Alexandrov L, Wunder JS, Andrulis IL, Malkin D, Behjati S, Shlien A. Rearrangement bursts generate canonical gene fusions in bone and soft tissue tumors. Science Aug 31;361(6405). pii: eaam8419. doi: 10.1126/science.aam8419, 2018. Rearrangement bursts generate canonical gene fusions in bone and soft tissue tumors.
    
2. Kratz CP, Achatz MI, Brugières L, Frebourg T, Garber JE, Greer MC, Hansford JR, Janeway KA, Kohlmann WK, McGee R, Mullighan CG, Onel K, Pajtler KW, Pfister SM, Savage SA, Schiffman JD, Schneider KA, Strong LC, Evans DGR, Wasserman JD, Villani A, Malkin D. Cancer screening recommendations for indiviudals with Li-Fraumeni Syndrome. Clinical Cancer Res 23(11):e38-e45, 2017. Cancer screening recommendations for indiviudals with Li-Fraumeni Syndrome.

3. Villani A, Shore A, Wasserman JD, Stephens D, Kim RH, Druker H, Gallinger B, Naumer A, Kohlman W, Novokmet A, Tabori U, Tijerin M, Greer M-LC, Finlay JF, Schiffman JD, Malkin D. Biochemical and imaging surveillance in TP53 mutation carriers with Li-Fraumeni syndrome: 11 year followup of a prospective observational study. Lancet Oncology Sep;17(9):1295-305, 2016. Biochemical and imaging surveillance in TP53 mutation carriers with Li-Fraumeni syndrome: 11 year followup of a prospective observational study.

4. Samuel N, Wilson G, Lemire M, Id Said B, Lou Y, Li W, Merino D, Novokmet A, Tran J, Nichols KE, Finlay JL, Choufani S, Remke M, Ramaswamy V, Cavalli FMG, Elser C, Meister L, Taylor MD, Tabori U, Irwin M, Weksberg R, Wasserman JD, Paterson A, Hansford JR, Achatz MIW, Hudson TJ, Malkin D. Genome-wide DNA methylation analysis reveals epigenetic dysregulation of microRNA-34A in TP53-associated cancer susceptibility. J Clinical Oncol 34(30): 3697-3704, 2016. Genome-wide DNA methylation analysis reveals epigenetic dysregulation of microRNA-34A in TP53-associated cancer susceptibility.

5. Malkin D, Strong LCS, Li FP, Fraumeni JF, Nelson CE, Kim DH, Kassel J, Gryka MA, Bischoff FZ, Tainsky MA, Friend SH: Germline p53 mutations in a familial syndrome of breast cancer, sarcomas and other neoplasms. Science 1990: 250: pp 1233-1238. Germline p53 mutations in a familial syndrome of breast cancer, sarcomas and other neoplasms.

Graduate Students

Camilla Giovino
Brianne Laverty
Safa Majee
Noel Wei Yang Ong
Pamela Psarianos
Vallijah Subasri
Frank Telfer