Professor LEUNG Suet Yi | suetyi@hkucc.hku.hk
Professor
MBBS HK; MD HK; FRCPath; FRCPA; FHKAM(Pathology)
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 studied the gene expression profile of a large series of gastric cancers using cDNA microarray, and have revealed the diversity of gene expression reflecting intrinsic properties of tumour and normal cells, tumour-stroma interaction and host immune response. Our team has also identified many novel prognostic markers that modify gastric cancer behaviour and affect patient outcome. The long term goal of our laboratory is to identify novel genes that are important for the causation of gastric cancer, the molecular mechanisms underlying their altered expression, and to explore the use of some of these genes as markers for early detection, prognostication or drug targets.
Our team has extensively characterized the genetic basis for the exceptionally high incidence of early-onset colorectal cancer (CRC) in Hong Kong. We have uncovered the mutation spectrum of germline DNA mismatch repair gene, and revealed a founder mutation that is common in the Southern Chinese population which originated between 22 and 103 generations ago. We have described the first example of heritable germline methylation of MSH2 gene promoter as a cause of hereditary colon cancer, and uncovered a novel mechanism of methylation induction and gene silencing through abrogation of transcriptional termination signal in an upstream neighbouring gene. These data have enabled our laboratory to formulate a rational strategy for genetic testing, management and prophylactic screening of early-onset colorectal cancer patients and their family. We have also studied in depth the role of the BRAF mutation in colorectal cancers, and discovered an interesting relationship between the BRAF mutation and various pathways of colorectal carcinogenesis. A long term interest of our laboratory has been to compare the molecular genetic and gene expression profile changes in different subtypes (sporadic versus hereditary, early-onset versus late-onset, microsatellite unstable versus stable) of colorectal cancer, with the aim to identify novel pathways of carcinogenesis and hereditary predisposition.
Research Grant
- RGC-Competitive Earmarked Research Grants in 1999, 2000, 2001, 2002, 2003, 2006 and 2008
- Hong Kong Cancer Fund
Awards and Honors
Croucher Senior Medical Research Fellowship (2007)
Outstanding Research Award, The University of Hong Kong (2007)
Research Output Prize, The University of Hong Kong (2007)
Outstanding Young Researcher Award, The University of Hong Kong (2001)
Selected Publication List:
Click here for detail publication list on PubMed
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.
Li VS, Yuen ST, Chan TL, Yan HH, Law WL, Yeung BH, Chan AS, Tsui WY, So S, Chen X, Leung SY. Frequent inactivation of axon guidance molecule RGMA in human colon cancer through genetic and epigenetic mechanisms. Gastroenterology 2009;137(1):176-87.
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 USA 2007, 104:15418–15423.
Chan TL, Yuen ST, Kong CK, Chan YW, Chan AS, Ng WF, Tsui WY, Lo MW, Tam WY, Li VS and Leung SY. Heritable germline epimutation of MSH2 in a family with hereditary nonpolyposis colorectal cancer. Nat Genet 2006, 38:1178-1183.
Leung SY, Yuen ST, Chu KM, Mathy JA, Li R, Chan AS, Law S, Wong J, Chen X, So S. Expression profiling identifies chemokine (C-C motif) ligand 18 as an independent prognostic indicator in gastric cancer. Gastroenterology 2004, 127:457-469.
Chan TL, Zhao W, Cancer Genome Project, Leung SY and Yuen ST. BRAF and KRAS mutations in colorectal hyperplastic polyps and serrated adenomas. Cancer Res 2003, 63:4878-4881.
Chan AS, Tsui WY, Chen X, Chu KM, Chan TL, Chan AS, Li R, So S, Yuen ST and Leung SY. Down-regulation of ID4 by promoter hypermethylation in gastric adenocarcinoma. Oncogene 2003, 22:6946-6953.
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, and Brown PO. Phospholipase A2 group IIA expression in gastric adenocarcinoma is associated with prolonged survival and less frequent metastasis. Proc Natl Acad Sci USA 2002, 99:16203-16208.
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, 62:6451-6455.
Leung SY, Yuen ST, Chung LP, Chu KM, Chan ASY and Ho JCI. hMLH1 promoter methylation and lack of hMLH1 expression in sporadic gastric carcinomas with high-frequency microsatellite instability. Cancer Res 1999, 59:159-164.