72P - Impact of extended panel of genes for germline cancer testing

Background

Traditional genetic screening was based previously on the analysis of classical high penetrance genes such as BRCA1 and BRCA2. In the context of our clinical practice in Dubai, individuals fulfilling the criteria are tested for germline mutations to subsequently establish the clinical management. Our current standard diagnostic approach focuses on sequencing 110 genes through NGS leading to increase the chance of finding the causal mutation and to the widespread clinical use of genes for germline cancer testing.

Methods

A total of 111 cases were tested in UAE with a traditional panel (BRCA1, BRCA2 and CHEK2) from October 2013 till September 2016. Then we have integrated extended panels (36 then 110 genes) from October 2016 till March 2023 and tested 509 cases. Median age was 47 years. Cases were referred for genetic testing mainly due to personal history of breast and ovarian cancer.

Results

Mutations in traditionally screened cases represent 8.1% for BRCA1, BRCA2 and 1% for CHEK2 for all types of panels. However extended panel analysis had a higher detection rate of pathogenic mutations compared to traditional analysis with an average increase of 7% in several genes mainly MUTYH, TP53, MLH1, RAD51D, PALB2 (respectively 2.6%, 0.8%, 0.8%, 0.6%, 0.6%). The heterogeneity of the newly detected mutations identified reinforces the value of using an extended hereditary panel. Further analysis will correlate the characteristics of germline mutations and their correlation with the tumor type and with the age group.

Conclusions

To our knowledge this is the first abstract from the MEA focusing on the impact of the analysis of extended panel of genes to patients with suspicion of hereditary cancer. Our findings reinforce the utility of extended panels involved in hereditary cancer predisposition in the diagnostic routine which may impact their clinical management. The use of this approach facilitates the detection of pathogenic mutations in non-BRCA1/2 genes and aided management. This will allow opportunities for enhanced surveillance and intervention in a range of tumors.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

IPS Genomix.

Funding

Has not received any funding.

Disclosure

S. Dawood: Financial Interests, Personal, Speaker, Consultant, Advisor: Newbridge, Caris Life Sciences, Janssen, BMS, Lilly, MSD, AstraZeneca, Pfizer, Novartis, Ipsen; Financial Interests, Personal, Other, Clinical studies: AZ; Financial Interests, Personal, Research Grant: MSD, Amgen. M. Wasfy, R. Khoury: Financial Interests, Personal, Full or part-time Employment: IPS Genomix.