Title:
Professor

Institute:
McGill University, Montreal General Hospital and Jewish General Hospital

Department:
Medical Genetics

Province:
Quebec

Training:
Postdoctorate, Cancer Genetics, Montreal General Hospital, Montreal, QC, Canada
Clinical Research Fellow, Human Immunogenetics Laboratory, Imperial Cancer Research Fund, London, UK
Honorary Research Fellow, Family Cancer Clinic, St-Mark’s Hospital, London, UK
PhD, Imperial Cancer Research Fund, University of London, UK
MBBS, University of London, London, UK
BSc, Anatomy, University of London, London, UK

Research interests:
Hereditary forms of cancer

Recognitions and awards:
James McGill Scholar (McGill University), Chercheur National (FRSQ)

Career highlights:
James McGill Professorship, McGill University
Scientific Director, International Hereditary Breast and Ovarian Cancer Symposium

Research Projects

Project title:
Assessing the contribution of spindle assembly checkpoint genes to colorectal neoplasia

Funding period:
2011-2013

Program:
Operating Grant (Basic Research)

Summary:
The spindle assembly checkpoint is a mechanism that ensures that daughter cells inherit a balanced copy of the genetic material from the mother cell during cell division. Many genes are involved in this process and we have recently shown that a mutation in one of these genes was the cause of multiple gastrointestinal cancers in a man with several cancers. The aim of our proposal is to study whether mutations or misregulation of this and other important genes with closely related functions in the spindle assembly checkpoint (SAC) pathway also influence the risk of developing colorectal cancers in other patients. This will be accomplished as a case-control study using DNA and cell lines derived from colorectal cancer patients and unaffected individuals serving as controls. We believe this study will provide us with the opportunity to gain new insight into the mechanisms involved in the earliest stages of gastrointestinal carcinogenesis and could provide unique knowledge to help develop novel early diagnosis tools and treatments.

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Project title:
A multimodal genomic analysis strategy to identify novel breast cancer genes

Funding period:
2011-2013

Program:
Operating Grant (Basic Research)

Summary:
Around 5-10% of women with breast cancer have a strong family history of the disease. In genetics clinics throughout Canada genetic testing in two genes called BRCA1 and BRCA2 is done on a routine basis to identify at risk women and offer them increased surveillance for breast cancer. However in many families, no mutations in  the BRCA1/2 genes can be found. Over the last 15 years there has been much effort to find new genes but it has proved difficult. We have designed a new combined genomic approach that involves scanning the whole genome to look for altered genes that are "underperforming", the premise being that these genes may have mutations which stop them from working properly. We will investigate plausible new candidate genes found by genome scanning using  a variety of conventional techniques to determine the likelihood that they are disease causing. We have shown that this approach is effective in identifying genes colon cancer and now wish to apply it to hereditary breast cancer.
  
CRS publications:

Chong G, Jarry J, Marcus V, Thiffault I, Winocour S, Monczak Y, Drouin R, Latreille J, Australie K,  Bapat B, Gordon PH,Giguère Y, Gologan A, Galiatsatos P,  Jass JR, Wong N, Zaor S,Palma L, Kasprzak L, Tischkowitz M, Foulkes WD. High Frequency of Exon Deletions and Putative Founder Effects in French Canadian LynchSyndrome Families. Human Mutation, 2009.

Yasmeen A, Bismar TA, Kandouz M, Foulkes WD, Desprez PY, Al Moustafa AE . E6/E7 of HPV type 16 promotes cell invasion and metastasis of human breast cancer cells. Cell Cycle. 2007 Jun;6(16):2038-42.

Lili Li, Susan McVety, Rami Younan, Ping Liang, Desirée Du Sart, Philip H. Gordon, Pierre Hutter, Frans B.L. Hogervorst, George Chong, and William D. Foulkes. Distinct Patterns of Germ-Line Deletions in MLH1and MSH2: The Implication of Alu epetitive Element in the Genetic Etiology of Lynch Syndrome (HNPCC). Human Mutation, 2006

Susan McVety, Lili Li, Isabelle Thiffault, Philip Gordon, Elizabeth Macnamara, Nora Wong, Karlene Australie, Lidia Kasprzak, George Chong, William D Foulkes. The value of multi-modal gene screening in HNPCC in Quebec: three mutations in mismatch repair genes that would have not been correctly identified by genomic DNA sequencing alone. Fam Cancer. 2006;5(1):21-8.

Sun S, Greenwood CM, Thiffault I, Hamel N, Chong G, Foulkes WD. The HNPCC associated MSH2*1906G-->C founder mutation probably originated between 1440 CE and 1715 CE in the Ashkenazi Jewish population. J Med Genet. 2005 Oct;42(10):766-8.

McVety S, Younan R, Li L, Gordon PH, Wong N, Foulkes WD, Chong G. Novel genomic insertion-- deletion in MLH1: possible mechanistic role for non-homologous end-joining DNA repair. Clin Genet. 2005 Sep;68(3):234-8.

McVety S, Li L, Gordon P, Chong G,Foulkes WD. Disruption of an exon splicing enhancer in exon 3 of MLH1 is the cause of HNPCC in a Quebec family. J Med Genet. 2006 Feb;43(2):153-6. Epub 2005 May 27.

Thiffault I, Hamel N, Pal T, McVety S, Marcus VA, Farber D, Cowie S, Deschênes J, Meschino W, Odefrey F, Goldgar D, Graham T, Narod S, Watters AK, MacNamara E, Du Sart D, Chong G, Foulkes WD.Germline truncating mutations in both MSH2 and BRCA2 in a single kindred. Br J Cancer. 2004 Jan 26;90(2):483-91.

Al Moustafa AE, Foulkes WD, Wong A, Jallal H, Batist G, Yu Q, Herlyn M, Sicinski P, Alaoui-Jamali MA. Cyclin D1 is essential for neoplastic transformation induced by both E6/E7 and E6/E7/ErbB-2 cooperation in normal cells. Oncogene 2004 Jul 1;23(30):5252-6.

Rapley EA, Barfoot R, Bonaïti-Pellié C, Chompret A, Foulkes W, Perusinghe N, Reeve A, Royer-Pokora B, Schumacher V, Shelling A, Skeen J, de Tourreil S, Weirich A, Pritchard-Jones K, Stratton MR, Rahman N. Evidence for susceptibility genes to familial Wilms tumour in addition to WT1, FWT1 and FWT2. Br J Cancer. 2000 Jul;83(2):177-83.

Rahman N, Arbour L, Houlston R, Bonaïti-Pellié C, Abidi F, Tranchemontagne J, Ford D, Narod S, Pritchard-Jones K, Foulkes WD, Schwartz C, Stratton MR. Penetrance of mutations in the familial Wilms tumor gene FWT1. J Natl Cancer Inst. 2000 Apr 19;92(8):650-2.

Sun S, Pollock PM, Liu L, Karimi S, Jothy S, Milner BJ, Renwick A, Lassam NJ, Hayward NK, Hogg D, Narod SA, Foulkes WD. CDKN2A mutation in a non-FAMMM kindred with cancers at multiple sites results in a functionally abnormal protein. Int J Cancer. 1997 Nov 14;73(4):531-6.

Past CRS projects/Projets SRC antérieurs :

1995 Cell-cycle inhibitors and familial cancer.

1997 Locating the familial Wilms' tumour gene (FWT1) by allelic association in French-Canadian children with Wilms' tumours.

1999 Locating the familial Wilms' tumour gene (FWT1) by allelic association in French-Canadian children with Wilms' tumours.

2001 Towards a molecular description of proteus syndrome.

2003 Molecular mechanisms that underlie exon deletions in hereditary non-polyposis colorectal cancer.