Validation of an NGS Panel Designed for Detection of Actionable Mutations in Tumors Common in Latin America

Journal
Journal of Personalized Medicine
ISSN
2075-4426
Date Issued
2021
Author(s)
Mauricio Salvo
Evelin González-Feliú
Jessica Toro
Iván Gallegos
Ignacio Maureira
Nicolás Miranda-González
Olga Barajas
Eva Bustamante
Mónica Ahumada
Alicia Colombo
Camilo Villamán
Carolina Ibañez
María Loreto Bravo
Verónica Sanhueza
M. Loreto Spencer
Gonzalo de Toro
Erik Morales
Carolina Bizama
Patricia García
Ana María Carrasco
Lorena Gutiérrez
Justo Lorenzo Bermejo
Ricardo A. Verdugo
Katherine Marcelain
Type
Resource Types::text::journal::journal article
Scopus ID
2-s2.0-85114777775
WoS ID
WOS:000699778600001
DOI
URL
URL Institutional Repository
Abstract
<jats:p>Next-generation sequencing (NGS) is progressively being used in clinical practice. However, several barriers preclude using this technology for precision oncology in most Latin American countries. To overcome some of these barriers, we have designed a 25-gene panel that contains predictive biomarkers for most current and near-future available therapies in Chile and Latin America. Library preparation was optimized to account for low DNA integrity observed in formalin-fixed paraffin-embedded tissue. The workflow includes an automated bioinformatic pipeline that accounts for the underrepresentation of Latin Americans in genome databases. The panel detected small insertions, deletions, and single nucleotide variants down to allelic frequencies of 0.05 with high sensitivity, specificity, and reproducibility. The workflow was validated in 272 clinical samples from several solid tumor types, including gallbladder (GBC). More than 50 biomarkers were detected in these samples, mainly in BRCA1/2, KRAS, and PIK3CA genes. In GBC, biomarkers for PARP, EGFR, PIK3CA, mTOR, and Hedgehog signaling inhibitors were found. Thus, this small NGS panel is an accurate and sensitive method that may constitute a more cost-efficient alternative to multiple non-NGS assays and costly, large NGS panels. This kind of streamlined assay with automated bioinformatics analysis may facilitate the implementation of precision medicine in Latin America.</jats:p>
Cite this document
Salvo, M., González-Feliú, E., Toro, J., Gallegos, I., Maureira, I., Miranda-González, N., Barajas, O., Bustamante, E., Ahumada, M., Colombo, A., Armisén, R., Villamán, C., Ibañez, C., Bravo, M. L., Sanhueza, V., Spencer, M. L., De Toro, G., Morales, E., Bizama, C., … Marcelain, K. (2021). Validation of an ngs panel designed for detection of actionable mutations in tumors common in latin america. Journal of Personalized Medicine, 11(9), 899. https://doi.org/10.3390/jpm11090899
Dataset(s)
Subjects
ngs-panel

; 

target therapies

; 

predictive biomarkers

; 

somatic variants

; 

gallbladder cancer

; 

latin america

; 

brca1 protein

; 

brca2 protein

; 

epidermal growth factor receptor

; 

formaldehyde

; 

k ras protein

; 

mammalian target of rapamycin

; 

nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase

; 

paraffin

; 

phosphatidylinositol 4,5 bisphosphate 3 kinase

; 

american

; 

article

; 

bioinformatics

; 

breast cancer

; 

chile

; 

controlled study

; 

gallbladder cancer

; 

gene expression

; 

gene frequency

; 

gene mutation

; 

genetic marker

; 

hedgehog signaling

; 

high throughput sequencing

; 

human

; 

human tissue

; 

indel mutation

; 

major clinical study

; 

personalized medicine

; 

pipeline

; 

reproducibility

; 

sensitivity and specificity

; 

single nucleotide polymorphism

; 

tumor volume

; 

whole exome sequencing

; 

workflow