What if we would use a diagnostic multi-cancer gene panel for opportunistic screening? A study in 2,090 Dutch familial cancer patients

Lennart Johansson, Krista van Dijk-Bos, Annemieke van der Hout, Alain Knopperts, Beike Leegte, Peter van den Akker, Klaas Kok, Irene van Langen, Morris Swertz, Rinse Weersma, Richard Sinke, Birgit Sikkema-Raddatz, Helga Westers, Rolf Sijmons

UMCG, Groningen, Netherlands

Abstract

Objectives

In familial cancer (FC) diagnostics, analysis of next-generation sequencing data typically focuses on genes known to be associated with the cancer type that prompted referral. Currently, however, it is debated whether opportunistic screening should be performed when sequence data is available for other genes. We aimed to determine how many secondary findings (SFs) would be detected in cancer-predisposing genes present in our FC gene panel if we offered opportunistic screening to patients within FC diagnostics.

Methods

We anonymously reanalyzed sequencing data of 2,090 FC patients for either 73 genes (original FC panel) or 85 genes (updated panel) for SNVs, indels and CNVs. To determine the background prevalence of pathogenic variants in FC genes, we screened 1,326 individuals from the general Dutch population.

Results

We detected SFs in 3.0% of patients (excluding heterozygous CHEK2 and MUTYH variants), and a (likely) pathogenic variant matching their family’s cancer type in 10.1% of patients. In the Dutch population cohort, 3.2% of individuals had a (likely) pathogenic variant in a cancer-predisposing gene.

Conclusions

Our results can assist in the design of future research programs on opportunistic screening. These programs are needed because there is not yet sufficient evidence to meet international screening program criteria.

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