Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study.

Human Mutation
A BorgJonine L Bernstein

Abstract

BRCA1 and BRCA2 screening in women at high-risk of breast cancer results in the identification of both unambiguously defined deleterious mutations and sequence variants of unknown clinical significance (VUS). We examined a population-based sample of young women with contralateral breast cancer (CBC, n=705) or unilateral breast cancer (UBC, n=1398). We identified 470 unique sequence variants, of which 113 were deleterious mutations. The remaining 357 VUS comprised 185 unique missense changes, 60% were observed only once, while 3% occurred with a frequency of >10%. Deleterious mutations occurred three times more often in women with CBC (15.3%) than in women with UBC (5.2%), whereas combined, VUS were observed in similar frequencies in women with CBC and UBC. A protein alignment algorithm defined 16 rare VUS, occurring at highly conserved residues and/or conferring a considerable biochemical difference, the majority located in the BRCA2 DNA-binding domain. We confirm a multiplicity of BRCA1 and BRCA2 VUS that occur at a wide range of allele frequencies. Although some VUS inflict chemical differences at conserved residues, suggesting a deleterious effect, the majority are not associated with an increased risk of CBC.

Citations

Jan 10, 2012·Breast Cancer Research and Treatment·Michelle G RathBarbara Burwinkel
Jun 6, 2012·PloS One·Peter MeyerBeyhan Ataseven
Aug 28, 2012·International Journal of Oncology·Srdjan NovakovićAleš Vakselj
Dec 12, 2013·Breast Cancer Research : BCR·Olivier HarismendyKelly A Frazer
Feb 4, 2014·International Journal of Genomics·Lewei Duan, Duncan C Thomas
Jul 8, 2011·Breast Cancer Research and Treatment·Mireia MenéndezConxi Lázaro
Jun 3, 2014·Cancer Investigation·Gulsah CecenerTurkkan Evrensel
Jul 15, 2015·Critical Reviews in Oncology/hematology·Sing Yu MoorcraftBrian A Walker
Jan 6, 2015·Genetic Epidemiology·Marinela Capanu, Venkatraman E Seshan
Feb 16, 2015·Breast Cancer Research and Treatment·Michelle W Wong-BrownRodney J Scott
Mar 20, 2012·The Journal of Molecular Diagnostics : JMD·Imma HernanMiguel Carballo
Sep 2, 2016·Journal of Biomolecular Structure & Dynamics·D Thirumal Kumar, C George Priya Doss
Jun 20, 2017·International Journal of Radiation Biology·Jonine L BernsteinPatrick Concannon
Sep 10, 2017·Physiological Genomics·Amy L PasternakDaniel L Hertz
Sep 1, 2017·Methods and Applications in Fluorescence·Yasaman-Sadat BorgheiMohammad Reza Ganjali
Oct 20, 2011·Genetic Epidemiology·Melanie A QuintanaDavid V Conti
Jul 10, 2018·Japanese Journal of Clinical Oncology·Shoko SakuradaNobuo Yaegashi
Sep 4, 2018·International Journal of Cancer. Journal International Du Cancer·Jingmei LiKamila Czene
Feb 11, 2020·International Journal of Cancer. Journal International Du Cancer·Liming SuYuntao Xie
May 2, 2019·Journal of Medical Case Reports·Mohammed Z ShariffMohammad A Hossain
Nov 2, 2019·Oncotarget·Takeshi TerashimaChigusa Morizane
Oct 2, 2019·International Journal of Molecular Sciences·Bohua WuEmil Alexov
May 14, 2020·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Romy L S MesmanMaaike P G Vreeswijk

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