AUTHOR=Dalens Lorraine , Niogret Julie , Kaderbhai Courèche Guillaume , Boidot Romain TITLE=Is There a Role for Large Exome Sequencing in the Management of Metastatic Non-Small Cell Lung Cancer: A Brief Report of Real Life JOURNAL=Frontiers in Oncology VOLUME=12 YEAR=2022 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.863057 DOI=10.3389/fonc.2022.863057 ISSN=2234-943X ABSTRACT=Introduction

Non-small-cell lung cancer (NSCLC) is one of the main causes of death by cancer worldwide. With the rise of targeted therapies, the search for molecular abnormalities is becoming a crucial step in the management of lung cancer. Whole exome sequencing (WES) is developing rapidly and is now accessible in routine care. However, its value, compared to smaller gene panels, remains unclear.

Methods

We conducted a retrospective analysis of all 281 patients with lung carcinoma referred to the Molecular Tumor Board of the Georges-François Leclerc Cancer Center (CGFL) between March 2015 and January 2018. We compared the results of standard molecular testing with the results of WES performed on every patient.

Results

WES highlighted many more mutations than smaller panels (mutations were found in 82 genes, while smaller panels found, at the most, mutations in 12 genes). Most of these mutations were class III or IV according to the ESCAT classification. The exome sensitivity also showed limitations, notably a slightly lower efficiency for common mutations, including classical EGFR mutations.

Conclusion

Small, targeted panels could be preferred over WES at the initial diagnosis of metastatic NSCLC. They are more sensitive for the identification of mutations on the most frequently mutated genes, such as ALK, BRAF, EGFR, ERBB2, KRAS or MET. Larger panels or WES could be useful at disease progression, to enlarge treatment possibilities by highlighting uncommon but potentially targetable mutations that are not covered by smaller, targeted panels.