Mutation pattern of EGFR gene in Peruvian patients with non-small cell lung cancer.

Abstract

e20615 Background: The correct characterization of EGFR mutations is crucial to the proper management of NSCLC patients due to the possibility to treat these patients with specific targeted therapies. Herein we report the incidence, mutation pattern and novel mutations of EGFR mutation in Peruvian NSCLC patients. Methods: Between 2016 and 2023 a total of 1489 NSCLC patients from public and private centers were referred to ONCOGENOMICS laboratory for somatic mutation testing. Next Generation Sequencing (NGS) was performed using the Ampliseq for Illumina FOCUS or Custom panel and run on the Illumina MiSeq. Raw data were processed automatically on the BaseSpace Sequence Hub (Illumina) and aligned to the hg19 reference genome The default limit of detection (LOD) was set at 5% allelic frequency (VAF) in tissue samples and 0.5% VAF in cfDNA samples. Results: The study included 1401 NSCLC patients, 61.8% were women. Clinical stages were distributed III (22.5%), IV (77.5%). All tumors were adenocarcinoma. Incidence of EGFR-mutated NSCLC was 33.4% (450), 68.9% were women. We found 519 EGFR mutations in 450 tumors. Classical or common EGFR mutations; L858R or ex19del corresponded to 86.4% with 331 and 383 cases, respectively and L858R or ex19del + T790M corresponded to 13.6% with 2 cases onset and 50 cases in progression. EGFR T790M de novo mutations were found in 4 cases onset. In one case at diagnosis was detected a T790M-like 3R mutant EGFR p.(C797S); c.2390G > C, a drug resistance point mutation in ex20.Non-classical or atypical EGFR mutations corresponded to 14.0% (63/450) of cases. Non-classical EGFR mutations were categorized as follows according to Janning et al.: (i) More frequent uncommon EGFR mutations - 39.7% (25/63) including G719X, S768I, E709X and L861Q (22/25); G719X + S768I (1/25); and combinations with classical EGFR mutation L858R + S768I (2/25). (ii) EGFR exon 20 insertions - 44.5% (28/63), including a novel mutation EGFR p.(769_770VDinsGFV);c.2308_2309ins. All were located in the loop following the C-helix. And (iii) very rare mutations - 15.9% (10/63) including very rare point mutations in ex19 (1/10), ex18del (4/10), ex19ins (1/10) and complex mutations (ex19del + very rare point mutation in ex19 (4/10).Two point mutation no reported previously were found, EGFR, ex19, p.(S752F);c.2255C > T and EGFR, ex19, p.(T751P);c.2251A > C, both as co-mutations with classical EGFR ex19del mutation. Conclusions: The present study underscores the value of NGS to optimally address EGFR mutations, specially the rare and novel ones due to its higher sensitivity and specificity compared to other techniques. This approach is particularly important for the Latin American population which is underrepresented in genomic databases. Clinical correlation of this genomic findings is ongoing.