Prediction of breast cancer risk based on flow variant analysis of circulating peripheral blood mononuclear cells.
Prediction of breast cancer risk based on flow variant analysis of circulating peripheral blood mononuclear cells.
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DOI：
10.1016/j.xhgg.2022.100085
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发表时间：
2022-04-14
期刊：
影响因子：
--
通讯作者：
Ostrer H
中科院分区：
文献类型：
--
作者：
Loke J;Alim I;Yam S;Klugman S;Xia LC;Gruber D;Tegay D;LaBella A;Onel K;Ostrer H
识别患乳腺癌的高危妇女可能会挽救生命。具有致病性遗传变异的患者可以开始进行早期检测、化学预防和/或预防性手术的监测计划。新诊断的癌症患者也可以使用基因组测序的结果来决定手术;因此，快速的结果周转时间至关重要。癌症风险B（CR-B）是一种使用流式变异试验评估变异体对DNA双链断裂修复影响的试验，应用于接受巧合基因组检测的两组受试者，从而评估灵敏度、特异性和准确性，以及注释不确定意义变异体（VUS）的实用性。在匹配的外周血单核细胞（PBMC）和淋巴母细胞（LCL）中比较了该测试，并在基因转移的LCL中进行了拯救测试。CR-B表型表现出双峰分布：CR-B+指示DSB修复缺陷，CR-B-指示野生型修复。当比较匹配的LCL和PBMC以及日间测试时，CR-B产生了高度可重复的结果。通过使用野生型cDNA表达质粒的基因转移拯救了CR-B−表型。CR-B−表型预测VUS为良性或可能为良性。CR-B可以代表一种快速的替代面板测序的妇女与癌症和确定妇女在高风险的癌症，是一个有用的辅助注释VUS。
Identifying women at high risk for developing breast cancer is potentially lifesaving. Patients with pathogenic genetic variants can embark on a program of surveillance for early detection, chemoprevention, and/or prophylactic surgery. Newly diagnosed cancer patients can also use the results of gene panel sequencing to make decisions about surgery; therefore, rapid turnaround time for results is critical. Cancer Risk B (CR-B), a test that uses flow variant assays to assess the effects of variants in the DNA double-strand break repair, was applied to two groups of subjects who underwent coincidental gene panel testing, thereby allowing an assessment of sensitivity, specificity and accuracy, and utility for annotating variants of uncertain significance (VUS). The test was compared in matched peripheral blood mononuclear cells (PBMCs) and lymphoblastoid cells (LCLs) and tested for rescue in LCLs with gene transfer. The CR-B phenotype demonstrated a bimodal distribution: CR-B+ indicative of DSB repair defects, and CR-B−, indicative of wild-type repair. When comparing matched LCLs and PBMCs and inter-day tests, CR-B yielded highly reproducible results. The CR-B− phenotype was rescued by gene transfer using wild-type cDNA expression plasmids. The CR-B− phenotype predicted VUS as benign or likely benign. CR-B could represent a rapid alternative to panel sequencing for women with cancer and identifying women at high risk for cancer and is a useful adjunct for annotating VUS.
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