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Dr CHAN Tsun Leung Chris |
Assistant Professor

Molecular Genetics of Colorectal Cancer

Awards and Honors


Research Description

My main research interests are in the epidemiology, molecular genetics and epigenetics of colorectal cancer (CRC). My research focuses on the genetic factors affecting the development of early-onset CRC. We have performed a series of research studies to illustrate the role of DNA mismatch repair genes and their association with high frequency of early-onset CRC in local population. Protocols have been set up for genetic diagnosis of a variety of familial CRC syndromes, including hereditary non-polyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP) etc., for the Hereditary Gastrointestinal Cancer Genetic Diagnosis Laboratory run by our research team in Queen Mary Hospital. Hundreds of at risk families have been screened under these studies. We have also described a microsatellite and chromosome stable (MACS) phenotype which is present in the group of early-onset CRC and generated the mutation spectrum of DNA mismatch repair genes in Hong Kong, the first and most comprehensive data available for Chinese population. Recently, we have additional evidence to demonstrate the contribution of founder mutation in a quarter of the germline mutations in our patients.

In addition, we have also participated in the identification of BRAF, a novel mutation in human cancers and have characterized its involvement in the adenoma-carcinoma sequence of colorectal cancer and its importance in serrated polyps. Currently, w e are trying to dissect the molecular pathways of CRC. This approach will help to improve our understanding of tumourigenesis of CRC and lead us to verify the possibility of alternative pathway, such as the serrated pathway, of CRC other than the well-known adenoma-carcinomas pathway. Last but not least, we are also actively involved in the investigation of allelic imbalance of gene expression as a cause of hereditary colorectal cancer.

Major Research Grants

RGC - Competitive Earmarked Research Grants

Michael Kadoorie Cancer Genetics Research Fund

Sir Michael and Lady Kadoorie Funded Research into Cancer Genetics

Selected Publications

Click here for detail publication list on PubMed

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.

Li VS, Wong CW, Chan TL , Chan AS, Zhao W, Chu KM, So S, Chen X, Yuen ST and Leung SY. Mutations of PIK3CA in gastric adenocarcinoma. BMC Cancer 2005, 5:29.

Chan TL , Chan YW, Ho JWC, Chan C, Chan ASY, Chan E, Lam PWY, Tse CW, Lee KC, Lau CW, Gwi E, Leung SY, Yuen ST. MSH2 c.1452-1455delAATG is a founder mutation and an important cause of hereditary non-polyposis colorectal cancer in the southern Chinese population. Am J Hum Genet 2004, 74(5):1035-1042.

Zhao W, Chan TL, Chu KM, Chan ASY, Stratton MR, Yuen ST, Leung SY. Mutations of BRAF and KRAS in gastric cancer and their association with microsatellite instability. Int J Cancer 2004, 108(1):167-169.

Chan TL , Zhao W, Cancer Genome Project, Leung SY, Yuen ST. BRAF and KRAS mutations in colorectal hyperplastic polyps and serrated adenomas. Cancer Res 2003, 63(16):4878-4881.

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): 6451-6455.

Chan TL , Curtis LJ, Leung SY, Farrington SM, Ho JWC, Chan ASY, Lam PWY, Tse CW, Dunlop MG, Wyllie AH, Yuen ST.  Early-onset colorectal cancer with stable microsatellite DNA and near-diploid chromosomes.  Oncogene 2001, 20(35):4871-4876.

Chan TL , Yuen ST, Ho JWC, Chan ASY, Kwan KYM, Ho SH, Chung LP, Leung SY.  A novel germline 1.8-kb deletion of hMLH1 mimicking alternative splicing: a founder mutation in the Chinese population. Oncogene 2001, 20(23):2976-2981.

Chan TL , Yuen ST, Chung LP, Ho JWC, Kwan KYM, Chan ASY, Ho JCY, Leung SY, Wyllie AH.  Frequent Microsatellite Instability and Mismatch Repair Gene Mutations in Young Chinese Patients with Colorectal Cancer. J Natl Cancer Inst 1999, 91(14):1221-1226.

Chan TL , Yuen ST, Chung LP, Ho JWC, Fan YW, Leung SY.  Germline hMSH2 and differential somatic mutations in patients with Turcot syndrome. Genes Chromosome Cancer 1999, 25(2):75-81.