Moran Olivia, Nikitina Dina, Royer Robert, Poll Aletta, Metcalfe Kelly, Narod Steven A, Akbari Mohammad R, Kotsopoulos Joanne
Familial Breast Cancer Unit, Women's College Research Institute, Women's College Hospital, 76 Grenville Street, 6th Floor, Toronto, ON, M5S 1B2, Canada.
Department of Nutritional Sciences, University of Toronto, 150 College Street, Toronto, ON, M5S 3E2, Canada.
Breast Cancer Res Treat. 2017 Jan;161(1):135-142. doi: 10.1007/s10549-016-4038-y. Epub 2016 Oct 31.
BRCA mutations contribute to about 20% of all hereditary breast cancers. With full-genome sequencing as the emerging standard for genetic testing, other breast cancer susceptibility genes have been identified and may collectively contribute to up to 30% of all hereditary breast cancers. We re-assessed women who had previously tested negative for a BRCA mutation when outdated techniques were used, and discuss the implications of identifying a mutation several years after initial genetic testing.
We evaluated the prevalence of mutations in 12 breast cancer susceptibility genes (including BRCA1 and BRCA2) in 190 breast cancer patients with a strong family history of breast cancer. These women had previously tested negative for mutations in the large coding exons of BRCA1 and BRCA2 using the protein truncation test (PTT) between the years of 1996 and 2013.
We identified pathogenic mutations in 17 of 190 (9%) women. Six mutations were detected in BRCA1 (n = 2) and BRCA2 (n = 4). Eleven mutations were found in other breast cancer susceptibility genes including CHEK2 (n = 5), PALB2 (n = 2), BLM (n = 2), ATM (n = 1) and TP53 (n = 1).
Among 190 breast cancer patients with a family history of the disease, and who previously received a negative result for BRCA mutations using the PTT, 17 (9%) women were found to carry a high-risk pathogenic mutation in a breast cancer susceptibility gene. Six of these women were BRCA mutation carriers who were missed previously. These findings support the rationale for updated genetic testing in patients who tested BRCA mutation negative using outdated techniques.
BRCA突变约占所有遗传性乳腺癌的20%。随着全基因组测序成为基因检测的新兴标准，已鉴定出其他乳腺癌易感基因，它们可能共同导致高达30%的遗传性乳腺癌。我们重新评估了那些曾因使用过时技术而BRCA突变检测呈阴性的女性，并讨论了在初次基因检测数年之后鉴定出突变的意义。
我们评估了190例有乳腺癌家族史的乳腺癌患者中12个乳腺癌易感基因（包括BRCA1和BRCA2）的突变率。这些女性在1996年至2013年间曾使用蛋白质截短试验（PTT）检测BRCA1和BRCA2的大编码外显子突变，结果为阴性。
我们在190名女性中的17名（9%）发现了致病突变。在BRCA1中检测到6个突变（n = 2），在BRCA2中检测到4个突变。在其他乳腺癌易感基因中发现了11个突变，包括CHEK2（n = 5）、PALB2（n = 2）、BLM（n = 2）、ATM（n = 1）和TP53（n = 1）。
在190例有乳腺癌家族史且此前使用PTT检测BRCA突变结果为阴性的乳腺癌患者中，发现17名（9%）女性携带乳腺癌易感基因的高风险致病突变。其中6名女性是之前漏检的BRCA突变携带者。这些发现支持了对使用过时技术检测BRCA突变阴性的患者进行更新基因检测的基本原理。
