Increased yield of actionable mutations using multi-gene panels to assess hereditary cancer susceptibility in an ethnically diverse clinical cohort

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• 作者：Charité ; Ricker^a ; ^b ; ¹ ; ^{Charite.Ricker@med.usc.edu" class="auth_mail" title="E-mail the corresponding author} ; Julie O. Culver^a ; ¹ ; Katrina Lowstuter^a ; Duveen Sturgeon^a ; Julia D. Sturgeon^a ; Christopher R. Chanock^a ; William J. Gauderman^c ; Kevin J. McDonnell^a ; ^b ; Gregory E. Idos^a ; ^b ; Stephen B. Gruber^a ; ^b ; ^c
• 关键词：Hereditary cancer ; cancer risk assessment ; multi-gene panels ; variants of uncertain significance ; ethnic minorities
• 刊名：Cancer Genetics
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：209
• 期：4
• 页码：130-137
• 全文大小：425 K

文摘

This study aims to assess multi-gene panel testing in an ethnically diverse clinical cancer genetics practice. We conducted a retrospective study of individuals with a personal or family history of cancer undergoing clinically indicated multi-gene panel tests of 6–110 genes, from six commercial laboratories. The 475 patients in the study included 228 Hispanics (47.6%), 166 non-Hispanic Whites (35.4%), 55 Asians (11.6%), 19 Blacks (4.0%), and seven others (1.5%).

Panel testing found that 15.6% (74/475) of patients carried deleterious mutations for a total of 79 mutations identified. This included 7.4% (35/475) of patients who had a mutation identified that would not have been tested with a gene-by-gene approach. The identification of a panel-added mutation impacted clinical management for most of cases (69%, 24/35), and genetic testing was recommended for the first degree relatives of nearly all of them (91%, 32/35). Variants of uncertain significance (VUSs) were identified in a higher proportion of tests performed in ethnic minorities.

Multi-gene panel testing increases the yield of mutations detected and adds to the capability of providing individualized cancer risk assessment. VUSs represent an interpretive challenge due to less data available outside of White, non-Hispanic populations. Further studies are necessary to expand understanding of the implementation and utilization of panels across broad clinical settings and patient populations.