Related Experiment Video
Updated: May 9, 2026
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Comprehensive molecular profiling of advanced NSCLC using NGS: Prevalence of druggable mutations and clinical trial
Roberto Serna-Blasco1, Pilar Mediavilla-Medel1, Karla Medina2
1Liquid Biopsy Laboratory, Medical Oncology Department. Instituto de Investigación Biomédica Puerta de Hierro - Segovia de Arana, Majadahonda, Comunidad de Madrid, Spain.
Background:
In Spain, next-generation sequencing (NGS) is currently available in a limited number of specialized centers and remains inaccessible to a significant proportion of patients. The ATLAS study aims to explore the tumor molecular profile beyond known EGFR mutations and ALK translocations using NGS on tumor biopsy samples.
Methods:
Patients with EGFR-sensitizing mutations or ALK translocations were excluded. A total of 455 patients with advanced non-small cell lung cancer (NSCLC) were enrolled from 22 Spanish hospitals. DNA and RNA were extracted from formalin-fixed paraffin-embedded samples, and libraries were prepared using the Oncomine Focus Assay. The Trialing app was used to identify active clinical trials in Spain.
Results:
Mutations were detected in 65.7 % of the cases. Local pathology assessments detected druggable mutations in only 7.9 % of cases, while centralized NGS testing increased this detection rate to 25.9 %. The most prevalent druggable alteration was KRAS G12C (53.6 %), followed by MET amplification (8.1 %) and MET exon 14 skipping (7.3 %). Additionally, 34.5 % of patients had molecular alterations matching clinical trials, offering potential treatment opportunities. Women had a significantly higher probability of harbouring druggable mutations (36 % vs. 20.3 %, p < 0.001), including the KRAS G12C which was significantly more frequent in females (22.6 % vs. 10 %). KRAS mutations were more common in adenocarcinomas and increased with tumor differentiation grade (p < 0.001 and p = 0.049, respectively). Likewise, ALK translocations, EGFR mutations, BRAF V600E, MET exon 14 skipping, and RET/ROS1 fusions were mainly found in adenocarcinomas whereas copy number variations were more frequent in squamous carcinomas (28.6 % vs. 15.1 %; p = 0.003) and in men (22 % vs. 11.6 %; p = 0.008).
Conclusion:
The ATLAS study demonstrates the utility of comprehensive NGS testing, which detects clinically relevant mutations in more than one-third of patients and may extend therapy options.
