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

Abstract

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.

Keywords: Hereditary cancer; cancer risk assessment; ethnic minorities; multi-gene panels; variants of uncertain significance.

Figure 1

Mutations detected in 475 patients, overall and by cancer site, illustrating yield of panels *Patient(s) with both a target mutation and panel-detected mutation are included in both categories

Figure 2

(a) Percentage of tests with a mutation identified as the number of genes on a panel test increases. (b) Percentage of tests with a variant of uncertain significance identified as the number of genes on a panel test increases.

Figure 2

(a) Percentage of tests with a mutation identified as the number of genes on a panel test increases. (b) Percentage of tests with a variant of uncertain significance identified as the number of genes on a panel test increases.