Open Access Research article

Contribution of the PALB2 c.2323C>T [p.Q775X] Founder mutation in well-defined breast and/or ovarian cancer families and unselected ovarian cancer cases of French Canadian descent

Marc Tischkowitz11023*, Nelly Sabbaghian12, Nancy Hamel4, Carly Pouchet5, William D Foulkes1245, Anne-Marie Mes-Masson67, Diane M Provencher68 and Patricia N Tonin149

Author Affiliations

1 Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montreal, Quebec, Canada

2 Lady Davis Institute, Segal Cancer Centre, Jewish General Hospital, Montreal, Quebec, Canada

3 Department of Medical Genetics, University of Cambridge, Cambridge, UK

4 The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada

5 Department of Medical Genetics, Jewish General Hospital, Montreal, Quebec, Canada

6 Centre de recherche du Centre hospitalier de l′Université de Montréal (CRCHUM)/Institut du cancer de Montréal, Montreal, Canada

7 Département de médicine, Université de Montréal, Montreal, Canada

8 Division de gynécologie oncologique, et Département d’obstétrique et gynécologie, Université de Montréal, Montreal, Canada

9 Department of Medicine, McGill University, Montreal, Quebec, Canada

10 Department of Medical Genetics, Addenbrooke’s Treatment Centre, Addenbrooke's Hospital, University of Cambridge, Box 134, Level 6, Hills Road, Cambridge, CB2 0QQ, UK

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BMC Medical Genetics 2013, 14:5  doi:10.1186/1471-2350-14-5

Published: 9 January 2013



The PALB2 c.2323C>T [p.Q775X] mutation has been reported in at least three breast cancer families and breast cancer cases of French Canadian descent and this has been attributed to common ancestors. The number of mutation-positive cases reported varied based on criteria of ascertainment of index cases tested. Although inherited PALB2 mutations are associated with increased risks of developing breast cancer, risk to ovarian cancer has not been fully explored in this demographically unique population.


We screened the PALB2 p.Q775X variant in 71 families with at least three cases of breast cancer (n=48) or breast and ovarian cancers (n=23) that have previously been found negative for at least the most common BRCA1 and BRCA2 mutations reported in the French Canadian population and in 491 women of French Canadian descent who had invasive ovarian cancer and/or low malignant potential tumors of the major histopathological subtypes.


We identified a PALB2 p.Q775X carrier in a breast cancer family, who had invasive ductal breast carcinomas at 39 and 42 years of age. We also identified a PALB2 p.Q775X carrier who had papillary serous ovarian cystadenocarcinoma at age 58 among the 238 serous subtype ovarian cancer cases investigated, who also had breast cancer at age 52.


Our findings, taken together with previous reports, support adding PALB2 c.2323C>T p.Q775X to the list of cancer susceptibility genes for which founder mutations have been identified in the French Canadian population.

PALB2; p.Q775X; p.Q775*; Hereditary breast cancer; Breast cancer risk; Ovarian cancer; Founder mutations; French Canadians