Citation: Alenezi, W.M.; Milano, L.; Fierheller, C.T.; Serruya, C.; Revil, T.; Oros, K.K.; Behl, S.; Arcand, S.L.; Nayar, P.; Spiegelman, D.; et al. The Genetic and Molecular Analyses of RAD51C and RAD51D Identifies Rare Variants Implicated in Hereditary Ovarian Cancer from a Genetically Unique Population. Cancers 2022, 14, 2251. https://doi.org/10.3390/ cancers14092251 Academic Editors: Melissa Southey, Tu Nguyen-Dumont and Ingrid Winship Received: 18 March 2022 Accepted: 20 April 2022 Published: 30 April 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). cancers Article The Genetic and Molecular Analyses of RAD51C and RAD51D Identifies Rare Variants Implicated in Hereditary Ovarian Cancer from a Genetically Unique Population Wejdan M. Alenezi 1,2,3 , Larissa Milano 4,5 , Caitlin T. Fierheller 1,2 , Corinne Serruya 2 , Timothée Revil 1,6 , Kathleen K. Oros 7 , Supriya Behl 1,2 , Suzanna L. Arcand 2 , Porangana Nayar 2,8 , Dan Spiegelman 1,9 , Simon Gravel 1,6 , Anne-Marie Mes-Masson 10,11 , Diane Provencher 10,12 , William D. Foulkes 1,2,7,13,14,15 , Zaki El Haffaf 10,16 , Guy Rouleau 1,9 , Luigi Bouchard 17,18,19 , Celia M. T. Greenwood 1,7,15,20 , Jean-Yves Masson 4,5 , Jiannis Ragoussis 1,6 and Patricia N. Tonin 1,2,14, * 1 Department of Human Genetics, McGill University, Montreal, QC H3A0C7, Canada; wagdan.alenizy@mail.mcgill.ca (W.M.A.); caitlin.fierheller@mail.mcgill.ca (C.T.F.); timothee.revil@mcgill.ca (T.R.); supriya.behl@mail.mcgill.ca (S.B.); dan.spiegelman@mcgill.ca (D.S.); simon.gravel@mcgill.ca (S.G.); william.foulkes@mcgill.ca (W.D.F.); guy.rouleau@mcgill.ca (G.R.); celia.greenwood@mcgill.ca (C.M.T.G.); ioannis.ragoussis@mcgill.ca (J.R.) 2 Cancer Research Program, Centre for Translational Biology, The Research Institute of McGill University Health Centre, Montreal, QC H4A3J1, Canada; corinne.serruya@affiliate.mcgill.ca (C.S.); suzanna.arcand@mail.mcgill.ca (S.L.A.); porangana.nayar@mail.mcgill.ca (P.N.) 3 Department of Medical Laboratory Technology, Taibah University, Medina 42353, Saudi Arabia 4 Department of Molecular Biology, Medical Biochemistry and Pathology, Laval University, Quebec City, QC G1V0A6, Canada; larissa.milano-de-souza@crchudequebec.ulaval.ca (L.M.); jean-yves.masson@crchudequebec.ulaval.ca (J.-Y.M.) 5 Genome Stability Laboratory, Centre de Recherche du Centre Hospitalier de l’Université de Québec, HDQ Pavilion, Oncology Axis, Quebec City, QC G1R2J6, Canada 6 McGill Genome Centre, McGill University, Montreal, QC H3A0G1, Canada 7 Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC H3T1E2, Canada; kathleen.klein@mail.mcgill.ca 8 Institute of Parasitology, McGill University, Montreal, QC H9X3V9, Canada 9 Montreal Neurological Institute, McGill University, Montreal, QC H3A2B4, Canada 10 Institut du Cancer de Montréal, Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montreal, QC H2X0A9, Canada; anne-marie.mes-masson@umontreal.ca (A.-M.M.-M.); diane.provencher.med@ssss.gouv.qc.ca (D.P.); ahmed.zaki.anwar.el.haffaf.med@ssss.gouv.qc.ca (Z.E.H.) 11 Département de Médecine, Université de Montréal, Montreal, QC H3T1J4, Canada 12 Division of Gynecologic Oncology, Université de Montréal, Montreal, QC H4A3J1, Canada 13 Department of Medical Genetics, McGill University Health Centre, Montreal, QC H4A3J1, Canada 14 Department of Medicine, McGill University, Montreal, QC H3G2M1, Canada 15 Gerald Bronfman Department of Oncology, McGill University, Montreal, QC H3A1G5, Canada 16 Service de Médecine Geénique, Centre Hospitalier de l’Université de Montréal, Montreal, QC H2X0A9, Canada 17 Department of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, QC J1K2R1, Canada; luigi.bouchard@usherbrooke.ca 18 Department of Medical Biology, Centres Intégrés Universitaires de Santé et de Services Sociaux du Saguenay-Lac-Saint-Jean Hôpital Universitaire de Chicoutimi, Saguenay, QC G7H7K9, Canada 19 Centre de Recherche du Centre Hospitalier l’Université de Sherbrooke, Sherbrooke, QC J1H5N4, Canada 20 Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC H3A1A2, Canada * Correspondence: patricia.tonin@mcgill.ca; Tel.: +1-514-934-1934 (ext. 44069) Simple Summary: We have investigated RAD51C and RAD51D, hereditary ovarian cancer risk genes, in French Canadians of Quebec, Canada. This population of Western European origins exhibits a unique genetic landscape as shown by the frequency of carriers of specific rare pathogenic variants. As studying French Canadians could facilitate the identification and interpretation of clinically relevant variants, we performed genetic analyses of RAD51C and RAD51D in this population comprised of cases with a family history of ovarian cancer or those who developed it at a young age. We identified candidate variants and then investigated them in other French Canadian study groups. Cancers 2022, 14, 2251. https://doi.org/10.3390/cancers14092251 https://www.mdpi.com/journal/cancers