Cancer Genetics

Cancer Genetics is committed to excellence in research, education and teaching in the field of hereditary cancer. Human genetics is now at the forefront of academic medicine and is changing the management of cancer patients. Its applicability to the management of individuals with, or at risk of, cancer has created the sub-specialty of clinical cancer genetics. For the past two decades, hereditary cancer has been a prominent feature of research at McGill University and Dr Foulkes and his team have contributed significantly to this effort.

Contact Information

william.foulkes [at] (Dr. William Foulkes)
Lab: (514) 934-1934 x 42032 at the MUHC - Glen Site
Lab: (514) 340-8222 x 23100 at the Jewish General Hospital

Important recent research findings of our Cancer Genetics group

Certain populations like the French Canadian population of Quebec are notable for the presence of founder mutations that are the result of their presence in a small number of original settlers. Our team has contributed significantly to the identification, characterization and clinical application of founder mutations in the breast cancer susceptibility genes BRCA1, BRCA2 and PALB2. Identification of these founder mutations has greatly facilitated genetic screening of at risk families in Quebec through the use of low-cost, targeted screening assays. More recently, we contributed to the identification of a new breast cancer susceptibility gene, RECQL (Cybulski et al, Nat Genet 2015 Jun; 47(6): 643-6).

The Quebec population is also being studied for founder mutations in colorectal cancer susceptibility genes. In collaboration with Dr. Gabriel Capella in Barcelona, Spain, we aim to identify novel, highly penetrant susceptibility genes for colorectal cancer using the latest sequencing technologies available. Our strategy to focus on founder populations will improve our chances of identifying recurrent mutations in each population while using the other population for validation of the candidate genes identified.

Our work with a hypercalcemic small cell ovarian cancer (SCCOHT) was also published in 2014 in Nature Genetics (Witkowski et al, Nat Genet 2014; 46(5):438-43. By performing whole exome sequencing on 3 families with multiple members affected by small cell cancer of the ovary, hypercalcemic type (SCCOHT), we discovered that inherited mutations in the SMARCA4 gene were segregating with the disease in these families. Sequencing of additional tumours, familial and sporadic in origin, revealed that all had loss of SMARCA4 expression resulting either from mutations or loss of heterozygosity, identifying SCCOHT as a monogenic disease. To follow up on these findings, we are collaborating with Dr. Sidong Huang in the Department of Biochemistry at McGill to study the methylomes and transcriptomes of SCCOHT tumours and cell lines to identify critical SMARCA4 target genes/networks.

Since 2009, our group contributed several manuscripts to the description of the DICER1 mutations and associated phenotypes in families affected with cystic nephroma, embryonal rhabdomyosarcomas, ovarian sex cord stromal tumours, and multinodular goiter, among others. More recently, our work on this syndrome has extended to the identification of somatic mutations in DICER1. There are several on-going projects in our laboratory using patient tumours and model systems aimed at elucidating the molecular events required for tumour development in carriers of hereditary DICER1 mutations.

We continue to explore the genetic etiology of various rare, familial tumours. Identifying predisposing mutations in a single family can be challenging, but the advent of next generation sequencing technologies has greatly facilitated the process. In collaboration with research groups at our local core facility, the McGill University and Genome Quebec Innovation Center, we have worked to optimize exome sequencing of formalin-fixed, paraffin-embedded tumours. We are now able to compare the exomes from the germ-line and the tumours of individual patients, thus enabling us to observe the genetic changes involved in the molecular evolution of tumour cells. We have collected several families with rare hereditary cancer phenotypes from the clinic and from the literature that are currently under investigation in our laboratory.

The clinical aspect of the program

Clinical cancer genetics services are offered at the Department of Medical Genetics, McGill University Health Centre and Cancer Genetic Services, Jewish General Hospital. There are several genetic counsellors working at both sites, who are involved with training genetic counselling students.

Education and Training

Dr. Foulkes curently has several graduate students. Students are based in the Department of Human Genetics.

Visiting scholars are welcome to join our group for extended visits.

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