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. 2022 Feb 21;12(1):2507.
doi: 10.1038/s41598-022-06376-4.

Half of germline pathogenic and likely pathogenic variants found on panel tests do not fulfil NHS testing criteria

Tala Andoni  1 , Jennifer Wiggins  2 , Rachel Robinson  3 , Ruth Charlton  3 , Michael Sandberg  4 , Rosalind Eeles  5
Affiliations

Half of germline pathogenic and likely pathogenic variants found on panel tests do not fulfil NHS testing criteria

Tala Andoni et al. Sci Rep. .

Abstract

Genetic testing for cancer predisposition has been curtailed by the cost of sequencing, and testing has been restricted by eligibility criteria. As the cost of sequencing decreases, the question of expanding multi-gene cancer panels to a broader population arises. We evaluated how many additional actionable genetic variants are returned by unrestricted panel testing in the private sector compared to those which would be returned by adhering to current NHS eligibility criteria. We reviewed 152 patients referred for multi-gene cancer panels in the private sector between 2014 and 2016. Genetic counselling and disclosure of all results was standard of care provided by the Consultant. Every panel conducted was compared to current eligibility criteria. A germline pathogenic / likely pathogenic variant (P/LP), in a gene relevant to the personal or family history of cancer, was detected in 15 patients (detection rate of 10%). 46.7% of those found to have the P/LP variants (7 of 15), or 4.6% of the entire set (7 of 152), did not fulfil NHS eligibility criteria. 46.7% of P/LP variants in this study would have been missed by national testing guidelines, all of which were actionable. However, patients who do not fulfil eligibility criteria have a higher Variant of Uncertain Significance (VUS) burden. We demonstrated that the current England NHS threshold for genetic testing is missing pathogenic variants which would alter management in 4.6%, nearly 1 in 20 individuals. However, the clinical service burden that would ensue is a detection of VUS of 34%.

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Conflict of interest statement

Professor Rosalind Eeles: 1. GU-ASCO meeting in San Francisco - Jan 2016 – Honorarium as speaker $500 2. RMH FR meeting – Nov 2017 – support from Janssen, honorarium as speaker £1100 (Title: Genetics and Prostate Cancer) 3. University of Chicago invited talk May 2018 – Honorarium as speaker $1000 4. EUR 200 educational honorarium paid by Bayer & Ipsen to attend GU Connect “Treatment sequencing for mCRPC patients within the changing landscape of mHSPC” at a venue at ESMO, Barcelona, 28 September 2019 5. Prostate Dx Advisory Panel – Member of external Expert Committee. 30th June 2002/3 hours/ £900. The remaining authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
The UK Cancer Genetics Group consensus for genes to be included on cancer panels. Figure created from Taylor et al..
Figure 2
Figure 2
Overall results of gene panel testing. Of note, the VUS rate does not include VUS detected in patients with P/LP variants.
Figure 3
Figure 3
Cancer predisposition genes detected, sub-divided by the type of variant detected.
Figure 4
Figure 4
Overall results of gene panel testing, grouped by fulfilment of eligibility criteria. The individual who was adopted was excluded from this calculation as accurate estimation of family history was not possible.
Figure 5
Figure 5
A detailed look at the patients with pathogenic / likely pathogenic variants: did they fulfil NHS eligibility criteria? In this study, the same number of P/LP variants were detected in patients who were eligible for genetic testing and those who were not.
Figure 6
Figure 6
Actionability of gene panel results for 13 patients.
Figure 7
Figure 7
NNS for all patients, the eligible cohort, and the ineligible cohort.
See this image and copyright information in PMC

References

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