Next generation sequencing (NGS) as a useful tool to identify clinically meaningful somatic and germinal variants in the early stages of non-small-cell lung cancer (NSCLC).

Le résumé fourni par la source

e20068 Background: This is an innovative project that aims to implement NGS to detect new genetic alterations in the early stages of NSCLC and their potential role as biomarkers of the tumoral evolution or monitoring NSCLC patients (p) who have initially undergone surgery. Methods: 15 surgical and blood samples were collected from surgically treated NSCLC p in stage I-IIIA. PBMCs and tumor samples were prepared using the TruSight Cancer sequencing Panel representing 94 genes associated to a cancer predisposition. PBMC and tumor DNA were sequenced on the Illumina System. Somatic variants taken from matched tumor-PBMC p samples was carried out with VarScan and MuTect, and the variants were selected according to the potential or known clinical relevance. P were followed-up and further blood samples were collected, thus both DFS and OS were analysed. Results: Histology: adenocarcinoma: 13 p and squamous tumors: 2 p. Tumoral stages: IA: 6p, IB: 2p, IIA: 4p, IIB: 2p and IIIA: 1 p. We have established a pipeline that allowed the identification of somatic and/or germinal mutations in paired samples from tumor and PBMC´s DNA. From the obtained variant data we found 37/94 (39,36%) genes from the Panel that presented any kind of frequent missense mutation associated with Germinal, LOH and/or somatic or splice sites disruption in at least one p. 3/37 (SLX4, NF1 and TP53) genes are represented in 30% of the p with some of the described mutations. For SLX4 and NF1 we found variations with uncertain clinical relevance. We highlight the significant and frequent presence of Fanconi anemia (FA) pathway mutations in 80% (12/15) of the analysed p. In addition, only 12/37 carried exclusively somatic variants in 11/15 analysed p. Conclusions: With the help of NGS technology we found pathologic variants potentially associated to the biology of NSCLC. The identified somatic mutations could be valuable potential markers to be used in further studies in ffcDNA, in terms of early detection and follow-up studies in NSCLC p. Although the Panel is limited and validation is needed, these findings may be useful for screening and relapsing this pathology and identifying novel therapeutical targets.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.