Phenotypes Associated With Constitutional EGFR Pathogenic Variants

A small proportion of lung cancers, particularly adenocarcinomas, is hereditary. Hereditary lung cancers occur in individuals with a genetic predisposition to the disease. It is important to remember that a proportion of non-small cell lung cancers develop in never smokers, illustrating the importance of other risk factors, such as pollution, radon or genetic factors. The overall proportion of hereditary lung adenocarcinomas is low, probably around 1%. On a French national scale, this still represents a few hundred cases per year.

EGFR is now an established susceptibility gene. EGFR variants are best known as somatic variants, as markers of sensitivity or resistance to tyrosine kinase inhibitors (TKIs).EGFR T790M, in particular, is usually an acquired variant seen in patients exposed to 1st and 2nd-generation tirosine kinase inihibitors (erlotinib, gefitinib, afatinib). But it is also sometimes constitutional, in which case it is somatically observed at diagnosis, when the patient has not be prescribed a TKI yet. Our research aims to gather data on French EGFR pathogenic variant carriers, i.e, index cases and relatives (affected and unaffected), and to describe the related phenotypes.

A retrospective, multicenter cohort study will be carried out,. The study aims to include 20 to 25 EGFR pathogenic variant carriers identified as such between 2018 and 2024. Data will be gathered from either paper or electronic patient files from the Oncogenetics clinic or laboratory, Eligible patients will be informed and given a possibility to opt out, in conformity with French legal requirements. Of note, all previously signed a consent form for genetic testing. . Each participating centre will be responsible for transcribing the pseudonymised data from its patients' medical records into a secure Excel file unique to each centre. The anonymized data obtained from the patient files will be electronically stored in a secure document accessible only to the principal investigator and a maximum of two close collaborators involved in the study. Data will be sent by participating centres to investigators from the Medical Genetics Department at APHP Sorbonne via the secure national RENATER platform.

Descriptive statistics will be done to describe the cohort's characeristics, e.g. mean/median age, proportion and type of somatic changes, prevalence of smoking in order to better characterize the phenotypes associated with EGFR.