Professor LEUNG Suet Yi

SY Leung

Department Chairperson
Chief of Service, Department of Pathology, Queen Mary Hospital
YW Kan Professor in Natural Sciences
Clinical Professor, Chair of Gastrointestinal Cancer Genetics and Genomics
Director, Hereditary Gastrointestinal Cancer Genetic Diagnosis Laboratory

  • MBBS (HK), MD (HK), FHKAM (Pathology), FHKCPath, FRCPath (UK), FRCPA

Molecular genetics and genomics of gastrointestinal tract cancer

Clinical Service

Director, Hereditary Gastrointestinal Cancer Genetic Diagnosis Laboratory

Research Description

My research interests are focused on the molecular genetics and genomics of gastric and colorectal cancers. We have performed comprehensive molecular profiling and integrative genomic studies on a large series of gastric and colorectal cancers using next-generation sequencing, expression microarray, methylation array and DNA SNP genotyping array. Our studies reveal the complex genomic landscape of gastric cancer and first identified many new gastric cancer driver genes. Examples include frequent mutation of ARID1A, a chromatic remodelling gene, in gastric cancers with MSI or EBV, and hotspot mutation of RHOA in diffuse type gastric cancer. Integrative genomic analysis revealed molecular subtype-specific patterns of genetic and epigenetic perturbations, many of them converging to target the same key cancer driver genes or pathways.

More recently, we have used patient tumour biopsies to establish a living bio-bank of organoid cultures, which are very similar to in vivo tumours. We have collected a large repertoire of organoids, encompassing different molecular subtypes, key driver gene alterations, stages of disease, as well as normal organoids, and have performed detailed morphological, genomic and transcriptomic analysis of them. Currently, we are testing the feasibility of large-scale drug sensitivity screening of organoids as a potential first-line guide for patient treatment. Overall, our organoid bio-bank, with linked genomic data, provides a valuable resource for understanding both cancer biology and anti-cancer drugs that may facilitate the development of precision cancer therapy.

In addition, our team has characterized the genetic basis of early- onset colorectal cancer (CRC) in Hong Kong and was the first to describe a new mechanism of MSH2 inactivation in Lynch Syndrome (a heritable form of CRC), involving large germline deletions in the EPCAM gene which is upstream of MSH2. Our findings have led to the incorporation of EPCAM deletion into the standard genetic diagnosis protocol for Lynch Syndrome worldwide. We now apply our findings to patient care, by providing a charitable genetic diagnosis service, including genetic testing and referral for prophylactic screening for early-onset or familial CRC patients. Our long-term goal is to enable genome-guided patient stratification, prognostication and personalised treatment of colorectal and gastric cancers by utilising genomic technology to identify novel pathways, biomarkers, drug targets and driver genes of carcinogenesis

Research Grant
  • RGC - General Research Fund in 1999, 2000, 2001, 2002, 2003, 2006, 2008 and 2010
  • Hong Kong Cancer Fund
  • Donation grant from Mr. Pan Su Tong
  • Theme-Based Research Scheme (TBRS)

Awards and Honors
  • YW Kan Endowed Professorship in Natural Sciences (2012)
  • Faculty Outstanding Research Output Award, Li Ka Shing Faculty of Medicine, The University of Hong Kong (2012, 2015, 2017,2019)
  • Outstanding Women Professionals Award (2014)
  • Croucher Senior Medical Research Fellowship (2007)
  • Outstanding Researcher Award, The University of Hong Kong (2007)
  • Research Output Prize, The University of Hong Kong (2007 and 2009)
  • Outstanding Young Researcher Award, The University of Hong Kong (2001)

Selected Publications

Click here for detail publication list

  • Yan HHN, Siu HC, Ho SL, Yue SSK, Gao Y, Tsui WY, Chan D, Chan AS, Wong JWH, Man AHY, Lee BCH, Chan ASY, Chan AKW, Hui HS, Cheung AKL, Law WL, Lo OSH, Yuen ST, Clevers H, Leung SY. Organoid cultures of early-onset colorectal cancers reveal distinct and rare genetic profiles. Gut. 2020; doi: 10.1136/gutjnl-2019-320019. 
  • Yan HHN, Siu HC, Law S, Ho SL, Yue SSK, Tsui WY, Chan D, Chan AS, Ma S, Lam KO, Bartfeld S, Man AHY, Lee BCH, Chan ASY, Wong JWH, Cheng PSW, Chan AKW, Zhang J, Shi J, Fan X, Kwong DLW, Mak TW, Yuen ST, Clevers H, Leung SY. A Comprehensive Human Gastric Cancer Organoid Biobank Captures Tumor Subtype Heterogeneity and Enables Therapeutic Screening. Cell Stem Cell. 2018;23(6):882-97 e11.
  • Yan HHN, Lai JCW, Ho SL, Leung WK, Law WL, Lee JFY, Chan AKW, Tsui WY, Chan ASY, Lee BCH, Yue SSK, Man AHY, Clevers H, Yuen ST, Leung SY. RNF43 germline and somatic mutation in serrated neoplasia pathway and its association with BRAF mutation. Gut. 2017;66(9):1645-56.
  • Wang K, Yuen ST, Xu J, Lee SP, Yan HH, Shi ST, Siu HC, Deng S, Chu KM, Law S, Chan KH, Chan AS, Tsui WY, Ho SL, Chan AK, Man JL, Foglizzo V, Ng MK, Chan AS, Ching YP, Cheng GH, Xie T, Fernandez J, Li VS, Clevers H, Rejto PA, Mao M, Leung SY. Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer. Nat Genet. 2014;46(6):573-82.
  • Wang K, Kan J, Yuen ST, Shi ST, Chu KM, Law S, Chan TL, Kan Z, Chan AS, Tsui WY, Lee SP, Ho SL, Chan AK, Cheng GH, Roberts PC, Rejto PA, Gibson NW, Pocalyko DJ, Mao M, Xu J, Leung SY. Exome sequencing identifies frequent mutation of ARID1A in molecular subtypes of gastric cancer. Nat Genet. 2011;43(12):1219-23.
  • Ligtenberg MJ, Kuiper RP, Chan TL, Goossens M, Hebeda KM, Voorendt M, Lee TY, Bodmer D, Hoenselaar E, Hendriks-Cornelissen SJ, Tsui WY, Kong CK, Brunner HG, van Kessel AG, Yuen ST, van Krieken JH, Leung SY, Hoogerbrugge N. Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3' exons of TACSTD1. Nat Genet. 2009;41(1):112-7.
  • Kosinski C, Li VS, Chan AS, Zhang J, Ho C, Tsui WY, Chan TL, Mifflin RC, Powell DW, Yuen ST, Leung SY, Chen X. Gene expression patterns of human colon tops and basal crypts and BMP antagonists as intestinal stem cell niche factors. Proc Natl Acad Sci U S A. 2007;104(39):15418-23.
  • Chan TL, Yuen ST, Kong CK, Chan YW, Chan AS, Ng WF, Tsui WY, Lo MW, Tam WY, Li VS, Leung SY. Heritable germline epimutation of MSH2 in a family with hereditary nonpolyposis colorectal cancer. Nat Genet. 2006;38(10):1178-83.
  • Chan TL, Zhao W, Leung SY, Yuen ST, Cancer Genome P. BRAF and KRAS mutations in colorectal hyperplastic polyps and serrated adenomas. Cancer Res. 2003;63(16):4878-81.
  • Yuen ST, Davies H, Chan TL, Ho JW, Bignell GR, Cox C, Stephens P, Edkins S, Tsui WW, Chan AS, Futreal PA, Stratton MR, Wooster R, Leung SY. Similarity of the phenotypic patterns associated with BRAF and KRAS mutations in colorectal neoplasia. Cancer Res. 2002;62(22):6451-5.
  • Leung SY, Chen X, Chu KM, Yuen ST, Mathy J, Ji J, Chan AS, Li R, Law S, Troyanskaya OG, Tu IP, Wong J, So S, Botstein D, Brown PO. Phospholipase A2 group IIA expression in gastric adenocarcinoma is associated with prolonged survival and less frequent metastasis. Proc Natl Acad Sci U S A. 2002;99(25):16203-8.
  • Leung SY, Yuen ST, Chung LP, Chu KM, Chan AS, Ho JC. hMLH1 promoter methylation and lack of hMLH1 expression in sporadic gastric carcinomas with high-frequency microsatellite instability. Cancer Res. 1999;59(1):159-64.