Kathy Chun

Dr. Chun obtained her undergraduate and graduate degrees from the University of Toronto prior to completing two post-doctoral clinical fellowships at the Hospital for Sick Children.

She is boarded with the Canadian College of Medical Geneticists (CCMG) in Molecular Genetics and in Cytogenetics and is an active member of the College.

She was the Head of the Cancer Cytogenetics Laboratory at the University Health Network for several years before moving to North York General Hospital, where she was the Director of Cytogenetics and Molecular Genetics for 11 years.

Dr. Chun is currently a Clinical Laboratory Director in Genome Diagnostics at The Hospital for Sick Children, where she is involved in clinical service and in translational research.

Dr. Chun has an interest in clinical laboratory quality management and has been an active member of the Genetics Scientific Committee of the Institute for Quality Management in Healthcare (IQMH) for many years, most currently as Chair.

She is also passionate about education and in particular about examinations and has been extensively involved in examinations with both the CCMG and CSMLS (Canadian Society of Medical Laboratory Science) for many years.

Research Synopsis

As a clinical cytogeneticist, molecular geneticist and a director of a clinical genetics laboratory, my research interests lie in the use of cytogenetic and molecular genetic technologies to study acquired disorders and constitutional disease, with a focus on test development that leads to practice changes and practice guidelines.

Genetic and genomic diagnostic testing has been evolving at a rapid pace for the last 20 years, initiated by the sequencing of the human genome in 2000 and fuelled by advances in new technologies such as fluorescence in situ hybridization (FISH), genomic microarrays and next generation sequencing (NGS).

The ability to test extensive regions of the human genome by these new technologies has and continues to drive understanding of the pathobiology of human disease. In addition, precision medicine is now fundamentally changing the delivery of healthcare, where we are moving away from a “one size fits all” approach and towards prevention and treatment strategies tailored to individuals, informed by specific genetic changes. My extensive experience in various patient care centres, each with a different patient focus, has afforded me the opportunity to enable the transition of new genomic findings to clinical genetic testing in different clinical arenas.

Since the discovery of the Philadelphia chromosome in 1960 as the genetic hallmark of chronic myelogenous leukemia (CML), thousands of cytogenetic and molecular genetic pathogenic variants have been shown to be diagnostic, prognostic or impact therapeutic options in cancer. However, there is often a significant gap between basic research discovery and clinically available tests that meet the time-sensitive needs of pathologists and oncologists to manage their patients.

A key interest and focus of mine has been to translate the advances in understanding the molecular basis of human cancers to a clinical test that has a direct impact on patient care. I have had a significant impact on hereditary breast and ovarian cancer (HBOC) testing in the province by developing a sequencing/MLPA test for BRCA1 and BRCA2, key genes in HBOC diagnostics. I then transitioned this test to a next-generation sequencing (NGS) panel. This work set the benchmark for HBOC testing in the province, both in terms of technology and test turnaround times. I was the co-lead in an international study that described the evidence-based clinical utility of genomic microarray analysis in CLL (chronic lymphocytic leukemia) diagnostics and prognostics and recommended its integration into clinical practice.

Currently, I am working with the Kids Cancer Sequencing Program (KiCS), led by Drs. Adam Shlien and David Malkin at the Hospital for Sick Children. The KiCS program is part of a national precision medicine program designed to bring genomic sequencing to every child and young adult with a hard-to-treat cancer. KiCS is the largest paediatric program in Canada and one of the few in the world to offer whole genome and transcriptome sequencing. I am leading the clinical validation and interpretation of copy number variants for this program. These results will be integrated into the clinical report with the sequence information. The information obtained through our NGS test will allow us to understand the cause of the cancer and to identify the tumour’s unique genetic fingerprint that informs prognosis and suggests targets for intervention.

Pregnancy is a joyful and exciting period for most couples, but it can also be a very stressful time when couples are anxiously awaiting test results that could tell them if their baby is healthy or not. Therefore, it is important to have test results as soon as possible to make management decisions that could impact the current pregnancy as well as future ones.

My interest in integrating new technologies into advancing and improving genetic prenatal diagnosis has been evidenced by my work on implementing QF-PCR (quantitative fluorescent PCR) as a new rapid aneuploidy detection test (RAD) test. Chromosome abnormalities are recognized as a common cause of miscarriage and congenital anomalies accounting for 50% - 70% of pregnancy losses in the first trimester. Trisomy of chromosomes 13, 18 or 21 represent the most common aneuploidies observed in the second or third trimester so it is important to detect these common aneuploidies in prenatal specimens to make informed management decisions.

I was the first in North America to establish QF-PCR as a clinical RAD test. QF-PCR employs microsatellite markers to detect the common aneuploidies. It has a turnaround time of 1 to 2 days, is inexpensive, capable of high specimen throughput, suitable for low quality/quantity specimens and detects maternal cell contamination and mosaicism. My work on developing QF-PCR was the catalyst in establishing QF-PCR in many centres across the country. QF-PCR is now the most common RAD test in Canada and has been endorsed by the SOGC (Society of Obstetricians and Gynaecologists of Canada) and the CCMG (Canadian College of Medical Geneticists) as the RAD test for women at increased risk of an aneuploid pregnancy.

Selected Publications

Dossa F, Metcalfe K, Sutradhar R, Little T, Eisen A, CHUN K, Meschino WS, Velsher L, Lerner Ellis J, Baxter NN. Cohort profile: the What Comes Next Cohort (WCNC) – a longitudinal study of health care utilization and outcomes after BRCA1 and BRCA2 testing. CMAJ Open. In press.

Ashfield T, McCready E, Shago M, Wang, H, Sinclair-Bourque E, Cappa E, Piche Marolt A and CHUN K. Practice patterns of prenatal and perinatal testing in Canadian cytogenetics laboratories. Prenat Diagn. 2021 Jun;41(7):843-854.

CHUN K, Wenger GD, Chaubey A, Dash DP, Kanagal-Shamanna R, Kanturci S, Kolhe R, Van Dyke DL, Wang L, Wolff DJ and Miron PM. Assessing copy number aberrations and copy-neutral loss-of-heterozygosity across the genome as best practice: An evidence-based review from the Cancer Genomics Consortium (CGC) working group for chronic lymphocytic leukemia. Cancer Genet. 2018 Dec;228-229:236-250.

Lebo MS, Zakoor KR, CHUN K, Speevak MD, Waye JS, McCready E, Parboosingh JS, Lamont RE, Feilotter H, Bosdet I, Tucker T, Young S, Karsan A, Charames GS, Agatep R, Spriggs EL, Chisholm C, Vasli N, Daoud H, Jarinova O, Tomaszewski R, Hume S, Taylor S, Akbari MR, Lerner-Ellis J and the Canadian Open Genetics Repository Working Group. Data sharing as a national quality improvement program: Reporting on BRCA1 and BRCA2 variant interpretation comparisons through the Canadian Open Genetics Repository (COGR). Genet Med. 2018 Mar;20(3):294-302.

Dawson AJ, Hryshko M, Konkin D, Bal S, Bernier D, Tomiuk M, Burnett S, Frosk P, Chodirker BN and CHUN K. Origin of a prenatal mosaic supernumerary neocentromeric derivative chromosome 13 determined by QF-PCR. Fetal Diagn Ther. 2013;33(1):75-78.

Cherry AM, Slovak ML, Campbell LJ, CHUN K, Eclache V, Haase D, Haferlach C, Hildebrandt B, Iqbal AM, Jhanwar SC, Ohyashiki K, Sole F, Vandenberghe P, VanDyke DL, Zhang Y, and Dewald GW. Will a peripheral blood (PB) sample yield the same diagnostic and prognostic cytogenetic data as the concomitant bone marrow (BM) in Myelodysplasia? Leuk Res. 2012 July;36(7):832-840. Impact Factor: 2.066. CA.

Speevak M, McGowan-Jordan J and CHUN K. The detection of chromosome anomalies by QF-PCR and residual risks as compared to G-banded analysis. Prenat Diagn. 2011 May;31(5):454-458

Joseph-George AM, He Y, Marshall CR, Wong RCC, MacDonald JR, Fahey CA, Chitayat D, CHUN K, Ryan G, Summers AM, Winsor EJ and Scherer SW. Euchromatic 9q13-q21 duplication variants are tandem amplifications of sequence reciprocal to 9q13-q21 deletions. J Med Genet. 2011 May;48:317-322. doi: 10.1136/jmg.2010.085662. Epub 2011 Mar 23. Available from: https://jmg.bmj.com/content/48/5/317.long. Impact Factor: 5.751. CA.

Allingham-Hawkins D, Chitayat D, Cirigliano V, Summers A, Tokunaga, Winsor E and CHUN K. Prospective validation of quantitative fluorescent polymerase chain reaction for rapid detection of common aneuploidies. Genet Med. 2011 Feb;13(2):140-147.

CHUN K, Hagemeijer A, Iqbal A and Slovak M. Implementation of standardized international karyotype scoring practices is needed to provide uniform and systematic evaluation for patients with Myelodysplastic Syndrome using IPSS criteria: an International Working Group on MDS Cytogenetics study. Leuk Res. 2010 Feb;34(2):160-165.

Appointments

Clinical Laboratory Director in Genome Diagnostics, The Hospital for Sick Children, Toronto