BACKGROUND: Known breast cancer-predisposing genes account for fewer than 25% of all familial breast cancer cases and further studies are required to find the remaining high- and moderate-risk genes. We set-out to couple linkage analysis using microsatellite marker data and sequence analysis of linked regions in 13 non-BRCA1/2 families in order to find novel susceptibility loci and high-penetrant genes. MATERIALS AND METHODS: Genotyping with 540 fluorescently-labeled microsatellite markers located on the 23 chromosomes at 7.25 cM resolution was used for primary linkage analysis and an additional 40 markers were used for fine-mapping of loci with a logarithm of odds (LOD) or heterogeneity LOD (HLOD) score greater than one. Whole-exome sequencing data of 28 members from all 13 families were used for the bioinformatics sequence analysis on the linked regions of these families. RESULTS: Linkage analysis identified three loci on chromosome 18q as a putative region of interest (overall LOD=1, HLOD=1.2). Sequencing analysis of the three linked regions on 18q and mutation prediction algorithms did reveal three probable damaging variants. CONCLUSION: Overall, our study identified three weakly linked loci on 18q and three probable damaging variants of interest in the 13 families with breast cancer. Copyright
BACKGROUND: Known breast cancer-predisposing genes account for fewer than 25% of all familial breast cancer cases and further studies are required to find the remaining high- and moderate-risk genes. We set-out to couple linkage analysis using microsatellite marker data and sequence analysis of linked regions in 13 non-BRCA1/2 families in order to find novel susceptibility loci and high-penetrant genes. MATERIALS AND METHODS: Genotyping with 540 fluorescently-labeled microsatellite markers located on the 23 chromosomes at 7.25 cM resolution was used for primary linkage analysis and an additional 40 markers were used for fine-mapping of loci with a logarithm of odds (LOD) or heterogeneity LOD (HLOD) score greater than one. Whole-exome sequencing data of 28 members from all 13 families were used for the bioinformatics sequence analysis on the linked regions of these families. RESULTS: Linkage analysis identified three loci on chromosome 18q as a putative region of interest (overall LOD=1, HLOD=1.2). Sequencing analysis of the three linked regions on 18q and mutation prediction algorithms did reveal three probable damaging variants. CONCLUSION: Overall, our study identified three weakly linked loci on 18q and three probable damaging variants of interest in the 13 families with breast cancer. Copyright
Authors: Xiang Jiao; Christos Aravidis; Rajeshwari Marikkannu; Johanna Rantala; Simone Picelli; Tatjana Adamovic; Tao Liu; Paula Maguire; Barbara Kremeyer; Liping Luo; Susanna von Holst; Vinaykumar Kontham; Jessada Thutkawkorapin; Sara Margolin; Quan Du; Johanna Lundin; Kyriaki Michailidou; Manjeet K Bolla; Qin Wang; Joe Dennis; Michael Lush; Christine B Ambrosone; Irene L Andrulis; Hoda Anton-Culver; Natalia N Antonenkova; Volker Arndt; Matthias W Beckmann; Carl Blomqvist; William Blot; Bram Boeckx; Stig E Bojesen; Bernardo Bonanni; Judith S Brand; Hiltrud Brauch; Hermann Brenner; Annegien Broeks; Thomas Brüning; Barbara Burwinkel; Qiuyin Cai; Jenny Chang-Claude; Fergus J Couch; Angela Cox; Simon S Cross; Sandra L Deming-Halverson; Peter Devilee; Isabel Dos-Santos-Silva; Thilo Dörk; Mikael Eriksson; Peter A Fasching; Jonine Figueroa; Dieter Flesch-Janys; Henrik Flyger; Marike Gabrielson; Montserrat García-Closas; Graham G Giles; Anna González-Neira; Pascal Guénel; Qi Guo; Melanie Gündert; Christopher A Haiman; Emily Hallberg; Ute Hamann; Patricia Harrington; Maartje J Hooning; John L Hopper; Guanmengqian Huang; Anna Jakubowska; Michael E Jones; Michael J Kerin; Veli-Matti Kosma; Vessela N Kristensen; Diether Lambrechts; Loic Le Marchand; Jan Lubinski; Arto Mannermaa; John W M Martens; Alfons Meindl; Roger L Milne; Anna Marie Mulligan; Susan L Neuhausen; Heli Nevanlinna; Julian Peto; Katri Pylkäs; Paolo Radice; Valerie Rhenius; Elinor J Sawyer; Marjanka K Schmidt; Rita K Schmutzler; Caroline Seynaeve; Mitul Shah; Jacques Simard; Melissa C Southey; Anthony J Swerdlow; Thérèse Truong; Camilla Wendt; Robert Winqvist; Wei Zheng; Javier Benitez; Alison M Dunning; Paul D P Pharoah; Douglas F Easton; Kamila Czene; Per Hall; Annika Lindblom Journal: Oncotarget Date: 2017-10-12