BACKGROUND: The genetic background in breast cancer families with colorectal and/or endometrial cancer is mostly unknown. The functional connection between MSH6 and the known breast cancer predisposition gene product BRCA1 suggests that the MSH6 gene may also play a role in breast cancer predisposition. METHODS: We analysed 38 breast cancer families with colorectal and/or endometrial cancer for germline mutations in MSH6. RESULTS: No disease associated mutations were detected among the breast cancer families. However, mutation analysis revealed a Glu995STOP mutation in an atypical HNPCC family. The same mutation was found in a patient with both breast and colorectal carcinoma in our previous study, and haplotype analysis confirmed a common ancestral origin. The Glu995STOP mutation was further examined in an extensive series of 245 colorectal and 142 breast carcinoma patients with a family history of breast, colorectal, and/or endometrial carcinoma, and in 268 healthy population controls, but none was found to carry the mutation. CONCLUSIONS: Our results suggest that MSH6 may not be the underlying gene in breast cancer families with a history of colorectal and/or endometrial cancer. The Glu995STOP founder mutation is not a familial breast cancer predisposition allele and makes only a limited contribution to colorectal cancer burden in Finland.
BACKGROUND: The genetic background in breast cancer families with colorectal and/or endometrial cancer is mostly unknown. The functional connection between MSH6 and the known breast cancer predisposition gene product BRCA1 suggests that the MSH6 gene may also play a role in breast cancer predisposition. METHODS: We analysed 38 breast cancer families with colorectal and/or endometrial cancer for germline mutations in MSH6. RESULTS: No disease associated mutations were detected among the breast cancer families. However, mutation analysis revealed a Glu995STOP mutation in an atypical HNPCC family. The same mutation was found in a patient with both breast and colorectal carcinoma in our previous study, and haplotype analysis confirmed a common ancestral origin. The Glu995STOP mutation was further examined in an extensive series of 245 colorectal and 142 breast carcinomapatients with a family history of breast, colorectal, and/or endometrial carcinoma, and in 268 healthy population controls, but none was found to carry the mutation. CONCLUSIONS: Our results suggest that MSH6 may not be the underlying gene in breast cancer families with a history of colorectal and/or endometrial cancer. The Glu995STOP founder mutation is not a familial breast cancer predisposition allele and makes only a limited contribution to colorectal cancer burden in Finland.
Authors: Luís S Santos; Susana N Silva; Octávia M Gil; Teresa C Ferreira; Edward Limbert; José Rueff Journal: Oncol Lett Date: 2018-02-21 Impact factor: 2.967
Authors: Benedito Mauro Rossi; Edenir Inêz Palmero; Francisco López-Kostner; Carlos Sarroca; Carlos Alberto Vaccaro; Florencia Spirandelli; Patricia Ashton-Prolla; Yenni Rodriguez; Henrique de Campos Reis Galvão; Rui Manuel Reis; André Escremim de Paula; Luis Gustavo Capochin Romagnolo; Karin Alvarez; Adriana Della Valle; Florencia Neffa; Pablo German Kalfayan; Enrique Spirandelli; Sergio Chialina; Melva Gutiérrez Angulo; Maria Del Carmen Castro-Mujica; Julio Sanchez de Monte; Richard Quispe; Sabrina Daniela da Silva; Norma Teresa Rossi; Claudia Barletta-Carrillo; Susana Revollo; Ximena Taborga; L Lena Morillas; Hélène Tubeuf; Erika Maria Monteiro-Santos; Tamara Alejandra Piñero; Constantino Dominguez-Barrera; Patrik Wernhoff; Alexandra Martins; Eivind Hovig; Pål Møller; Mev Dominguez-Valentin Journal: BMC Cancer Date: 2017-09-05 Impact factor: 4.430