The goal of this observational study is to describe the prevalence of germ line-pathogenic variants in Mexican patients with lung adenocarcinoma.

The main questions it aims to answer are:

1. What is the prevalence of pathogenic variants in genes associated with lung adenocarcinoma in Mexican patients younger than fifty?
2. Which clinical-pathological characteristics are associated with germ-line pathogenic variants in patients with lung adenocarcinoma?
3. How actionable somatic mutations are associated with germ line-pathogenic variants of patients with lung adenocarcinoma?

Participants will be asked to sign an informed consent; after that, they will be instructed to donate 10 ml of peripheral blood by venipuncture in the morning and before the patient has taken morning medication and the first meal, following a period of 8-12 hr fasting.

This is an observational, descriptive, and longitudinal study.

The sample size was calculated with a proportion difference formula for a known population, considering the Local Institutional Personalized Medicine Laboratory tests 100 blood samples per year from patients with non-small cell lung cancer (NSCLC). It was considered a 95% confidence level and an 80% power. In addition, a 10% loss in follow-up was estimated.

After reviewing the inclusion and exclusion criteria, signing the informed consent, and peripheral blood sampling. Total DNA (tDNA) will be extracted using the DNAeasy Blood & Tissue (Qiagen) kit.

Likewise, for the determination of pathogenic variants, the Sophia HCS Community panels (Sophia genetics) will be used to carry out Next-generation (NGS) sequencing in a NextSeq 550 (Illumina) platform.

To determine the clinical significance of genomic variants, the data analysis will be performed on the SOPHiA Alamut™ Visual Plus which is a comprehensive, full genome browser for efficient and user-friendly variant interpretation.

Inclusion Criteria:

• Both sexes
• ≥ 16 years old, according the institutional protocols for new patients admittances.
• histologically confirmed lung adenocarcinoma (LUAD)
• Signed written informed consent form
• A life expectancy greater than 8 weeks.
• Histologically confirmed LUAD and one of the following conditions: i) LCFH, defined as having one first-degree relative (FDR) or two or more second-degree relatives with LC, irrespective of the age at diagnosis. ii) Age at diagnosis ≤50 years, or ≤60 with a pack-years index. iii) Presence of ≥1 AGAs (EGFR, ALK, ROS1, KRAS, BRAF, MET exon 14 skipping, or RET).

Exclusion Criteria:

• A sample of peripheral blood that is not accessible.
• Insufficient clinical pathological information in the electronic clinical record.

Elimination Criteria:

• Withdrawal
• Insufficient DNA quality and quantity for genomic sequencing analyses.
• Lost of follow up

Patients with lung adenocarcinoma treated in the Thoracic Oncology Unit of the National Institute of Cancer.