Kast Karin, Wimberger Pauline, Arnold Norbert
Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany.
National Center for Tumor Diseases (NCT), Partner Site Dresden, Dresden, Germany.
Arch Gynecol Obstet. 2018 Feb;297(2):279-280. doi: 10.1007/s00404-017-4631-2. Epub 2018 Jan 4.
Classification of variants of unknown significance (VUS) in the breast cancer genes BRCA1 and BRCA2 changes with accumulating evidence for clinical relevance. In most cases down-staging towards neutral variants without clinical significance is possible.
We searched the database of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC) for changes in classification of genetic variants as an update to our earlier publication on genetic variants in the Centre of Dresden. Changes between 2015 and 2017 were recorded.
In the group of variants of unclassified significance (VUS, Class 3, uncertain), only changes of classification towards neutral genetic variants were noted. In BRCA1, 25% of the Class 3 variants (n = 2/8) changed to Class 2 (likely benign) and Class 1 (benign). In BRCA2, in 50% of the Class 3 variants (n = 16/32), a change to Class 2 (n = 10/16) or Class 1 (n = 6/16) was observed. No change in classification was noted in Class 4 (likely pathogenic) and Class 5 (pathogenic) genetic variants in both genes. No up-staging from Class 1, Class 2 or Class 3 to more clinical significance was observed.
All variants with a change in classification in our cohort were down-staged towards no clinical significance by a panel of experts of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC). Prevention in families with Class 3 variants should be based on pedigree based risks and should not be guided by the presence of a VUS.
随着乳腺癌基因BRCA1和BRCA2中意义未明变异（VUS）临床相关性证据的不断积累，其分类也在发生变化。在大多数情况下，有可能将其下调为无临床意义的中性变异。
我们检索了德国遗传性乳腺癌和卵巢癌联盟（GC-HBOC）的数据库，以了解基因变异分类的变化，作为我们早期关于德累斯顿中心基因变异的出版物的更新。记录了2015年至2017年之间的变化。
在意义未分类变异组（VUS，3类，不确定）中，仅注意到向中性基因变异的分类变化。在BRCA1中，25%的3类变异（n = 2/8）变为2类（可能良性）和1类（良性）。在BRCA2中，50%的3类变异（n = 16/32）观察到变为2类（n = 10/16）或1类（n = 6/16）。在这两个基因的4类（可能致病）和5类（致病）基因变异中，未观察到分类变化。未观察到从1类、2类或3类上调至更具临床意义的情况。
在我们的队列中，所有分类发生变化的变异均被德国遗传性乳腺癌和卵巢癌联盟（GC-HBOC）的专家小组下调为无临床意义。对具有3类变异的家族进行预防应基于系谱风险，而不应受VUS的存在所指导。
