Hong Joohyun, Lee Jiyun, Kwon Minsuk, Kim Ji-Yeon, Kim Jong-Won, Ahn Jin Seok, Im Young-Hyuck, Park Yeon Hee
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.
Department of Laboratory Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.
Diagnostics (Basel). 2021 Feb 22;11(2):370. doi: 10.3390/diagnostics11020370.
Genetic diagnosis for human epidermal growth factor receptor 2-negative metastatic breast cancer patients with the germline (gBRCA) mutation has been emphasized since the development of polyadenosine diphosphate-ribose polymerase inhibitors. Myriad Genetics, Inc.'s (Salt Lake City, UT, USA) companion diagnostics service is almost exclusively used for genetic testing. The aim of this study was to compare the results of germline mutation tests returned by a local laboratory and those performed by Myriad. Between April 2014 and February 2018, 31 patients with gBRCA 1/2 mutation test results from both Samsung Medical Center (Seoul, Korea) and Myriad were enrolled. "Discordant: Opposite classification" was observed for only one among 27 (3.7%). This discrepancy was due to the detection of a deleterious large genomic rearrangement of by Myriad. Samsung Medical Center performed multiple ligation-dependent probe amplifications (MLPA) to detect large genomic rearrangements only in high-risk patients. This one case was not suspected as high risk and MLPA was not performed. The concordant rate was 74.1% for all 27 patients. "Discordant: Laboratory's uncertain classification" was found in 22.2% of the sample (six patients). All discrepancies were generated during interpretation of gene sequencing. Further studies and standardization of genetic testing for genes are required.
自从聚腺苷二磷酸核糖聚合酶抑制剂问世以来,针对携带种系(gBRCA)突变的人表皮生长因子受体2阴性转移性乳腺癌患者的基因诊断备受关注。美国犹他州盐湖城的Myriad Genetics公司的伴随诊断服务几乎被专门用于基因检测。本研究的目的是比较当地一家实验室返回的种系突变检测结果与Myriad公司所做检测的结果。在2014年4月至2018年2月期间,纳入了31例来自韩国首尔三星医疗中心且同时有Myriad公司gBRCA 1/2突变检测结果的患者。在27例患者中仅1例(3.7%)观察到“不一致:相反分类”。这种差异是由于Myriad公司检测到一个有害的大基因组重排。三星医疗中心仅对高危患者进行多重连接依赖探针扩增(MLPA)以检测大基因组重排。这例患者未被怀疑为高危,因此未进行MLPA检测。27例患者的总体一致率为74.1%。在22.2%的样本(6例患者)中发现“不一致:实验室不确定分类”。所有差异均在BRCA基因测序解读过程中产生。需要对BRCA基因的基因检测进行进一步研究和标准化。