Multigene Panel Testing Detects Equal Rates of Pathogenic BRCA1/2 Mutations and has a Higher Diagnostic Yield Compared to Limited BRCA1/2 Analysis Alone in Patients at Risk for Hereditary Breast Cancer
Multigene Panel Testing Detects Equal Rates of Pathogenic BRCA1/2 Mutations and has a Higher Diagnostic Yield Compared to Limited BRCA1/2 Analysis Alone in Patients at Risk for Hereditary Breast Cancer
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DOI：
10.1245/s10434-015-4754-2
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发表时间：
2015-10-01
影响因子：
3.7
通讯作者：
Banks, Kimberly C.
中科院分区：
文献类型：
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作者：
Kapoor, Nimmi S.;Curcio, Lisa D.;Banks, Kimberly C.
背景最近引入的多基因面板测试，包括BRCA 1和BRCA 2基因的遗传性癌症风险，提出了关注的能力，检测所有有害的BRCA 1/2突变相比，旧的方法依次测试BRCA 1/2分别。本研究的目的是评估致病性BRCA 1/2突变和变异的不确定意义（VUS）之间的遗传检测和多基因检测的新方法的限制性算法。回顾性收集了在同一机构的三个地点之一接受基因检测的966名患者的数据。将仅接受BRCA 1/2检测的患者（有限组，n = 629）与接受5-43个癌症相关基因的多基因检测的患者（小组组，n = 337）的检测结果进行比较。在37例患者中发现了有害的BRCA 1/2突变，限制组和面板组之间的发生率相当（分别为4.0%和3.6%，p = 0.86）。39例患者有BRCA 1/2 VUS，限制组和面板组的发生率相似（分别为4.5%和3.3%，p = 0.49）。在多变量分析中，两组之间BRCA 1/2突变或VUS的检测没有差异。在接受组检测的患者中，另外3.9%（n = 13）的患者存在非BRCA致病性突变，13.4%（n = 45）的患者存在非BRCA VUS。PALB 2、CHEK 2和ATM突变是最常见的非BRCA突变。多基因面板测试检测致病性BRCA 1/2突变在相同的速率作为有限的测试，并提高诊断率。小组测试增加VUS率，主要是由于非BRCA基因。有遗传性乳腺癌风险的患者可以安全地从前期、更有效的多基因面板测试中受益。
Background. Recently introduced multigene panel testing including BRCA1 and BRCA2 genes for hereditary cancer risk has raised concerns with the ability to detect all deleterious BRCA1/2 mutations compared to older methods of sequentially testing BRCA1/2 separately. The purpose of this study was to evaluate rates of pathogenic BRCA1/2 mutations and variants of uncertain significance (VUS) between previous restricted algorithms of genetic testing and newer approaches of multigene testing.Methods. Data was collected retrospectively from 966 patients who underwent genetic testing at one of three sites from a single institution. Test results were compared between patients who underwent BRCA1/2 testing only (limited group, n = 629) to those who underwent multigene testing with 5-43 cancer-related genes (panel group, n = 337).Results. Deleterious BRCA1/2 mutations were identified in 37 patients, with equivalent rates between limited and panel groups (4.0 vs. 3.6 %, respectively, p = 0.86). Thirty-nine patients had a BRCA1/2 VUS, with similar rates between limited and panel groups (4.5 vs. 3.3 %, respectively, p = 0.49). On multivariate analysis, there was no difference in detection of either BRCA1/2 mutations or VUS between both groups. Of patients undergoing panel testing, an additional 3.9 % (n = 13) had non-BRCA pathogenic mutations and 13.4 % (n = 45) had non-BRCA VUSs. Mutations in PALB2, CHEK2, and ATM were the most common non-BRCA mutations identified.Conclusions. Multigene panel testing detects pathogenic BRCA1/2 mutations at equivalent rates as limited testing and increases the diagnostic yield. Panel testing increases the VUS rate, mainly as a result of non-BRCA genes. Patients at risk for hereditary breast cancer can safely benefit from up-front, more efficient, multigene panel testing.