Biomarker testing for advanced lung cancer by next-generation sequencing; a valid method to achieve a comprehensive glimpse at mutational landscape
Appl. cancer res
; 40: 1-12, Oct. 19, 2020. tab, ilus
Artigo
em Inglês
| LILACS, Inca
| ID: biblio-1281498
Biblioteca responsável:
BR30.1
Localização: BR30.1
ABSTRACT
Background:
Next-generation sequencing (NGS) based assay for finding an actionable driver in non-small-cell lung cancer is a less used modality in clinical practice. With a long list of actionable targets, limited tissue, arduous single-gene assays, the alternative of NGS for broad testing in one experiment looks attractive. We report here our experience with NGS for biomarker testing in hundred advanced lung cancer patients.Methods:
Predictive biomarker testing was performed using the Ion AmpliSeq™ Cancer Hotspot Panel V2 (30 tumors) and Oncomine™ Solid Tumor DNA and Oncomine™ Solid Tumor Fusion Transcript kit (70 tumors) on IonTorrent sequencing platform.Results:
One-seventeen distinct aberrations were detected across 29 genes in eighty-six tumors. The most commonly mutated genes were TP53 (43% cases), EGFR (23% cases) and KRAS (17% cases). Thirty-four patients presented an actionable genetic variant for which targeted therapy is presently available, and fifty-two cases harbored non-actionable variants with the possibility of recruitment in clinical trials. NGS results were validated by individual tests for detecting EGFR mutation, ALK1 rearrangement, ROS1 fusion, and c-MET amplification. Compared to single test, NGS exhibited good agreement for detecting EGFR mutations and ALK1 fusion (sensitivity- 88.89%, specificity- 100%, Kappa-score 0.92 and sensitivity- 80%, specificity- 100%, Kappa-score 0.88; respectively). Further, the response of patients harboring tyrosine kinase inhibitor (TKI) sensitizing EGFR mutations was assessed. The progression-free-survival of EGFR positive patients on TKI therapy, harboring a concomitant mutation in PIK3CAmTOR and/or RAS-RAF-MAPK pathway gene and/or TP53 gene was inferior to those with sole-sensitizing EGFR mutation (2 months vs. 9.5 months, P = 0.015).Conclusions:
This is the first study from South Asia looking into the analytical validity of NGS and describing the mutational landscape of lung cancer patients to study the impact of co-mutations on cancer biology and treatment outcome. Our study demonstrates the clinical utility of NGS testing for identifying actionable variants and making treatment decisions in advanced lung cancer
Texto completo:
Disponível
Coleções:
Bases de dados internacionais
Temas:
Geral
/
Tipos de Câncer
/
Pulmão
Base de dados:
LILACS
/
PrevCan
Assunto principal:
Proto-Oncogenes
/
Biomarcadores Tumorais
/
Carcinoma Pulmonar de Células não Pequenas
/
Sequenciamento de Nucleotídeos em Larga Escala
/
Neoplasias Pulmonares
/
Mutação
Tipo de estudo:
Prognostic_studies
Limite:
Feminino
/
Humanos
/
Masculino
Idioma:
Inglês
Revista:
Appl. cancer res
Assunto da revista:
Neoplasias
Ano de publicação:
2020
Tipo de documento:
Artigo
País de afiliação:
Índia
Instituição/País de afiliação:
Department of Laboratory and Transfusion Services/IN
/
Department of Laboratory/IN
/
Department of Medical Oncology/IN
/
Department of Research/IN
Similares
MEDLINE
...
LILACS
LIS