Genomic alterations of plasma cell-free DNAs in small cell lung cancer and their clinical relevance

Lung Cancer : Journal of the International Association for the Study of Lung Cancer
Meijun DuLiang Wang

Abstract

To identify genomic variations in cell-free DNA (cfDNA) and evaluate their clinical utility in small cell lung cancer (SCLC). We performed whole genome sequencing using plasma cfDNAs derived from 24 SCLC patients for copy number variation (CNV) analysis, and targeted sequencing using 17 pairs of plasma cfDNA and their matched gDNA for mutation analysis. We defined somatic mutations by comparing cfDNA to its matched gDNA with 5% variant alleles as the cutoff for mutation calls. We applied Kaplan-Meier to correlate the genomic alterations with overall survival (OS) and progression-free survival (PFS). We observed widespread somatic copy-number alterations and mutations, including amplification of MYC at 8q24, FGF10 at 5p13, SOX2 at 3q26 and FGFR1 at 8p12, as well as deletion of TP53 at 17p13, RASSF1 at 3p21.3, RB1 at 13q14.2, FHIT at 3p14, and PTEN at 10q23. The most frequent mutations were genes involved in chromatin regulation (KMT2D, ARID1A, SETBP1 and PBRM1), PI3K/MTOR pathway(MTOR,PIK13G), Notch1 signalling pathway (NOTCH1), and DNA repair related gene ATRX. Kaplan-Meier analysis revealed poor OS and PFS in patients with somatic mutations in gene SETBP1 (P = 0.0061/0.0264, HR = 4.785/3.841, 95% CI = 2.014-28.25/1.286-16.58) ...Continue Reading

Citations

Oct 15, 2019·Expert Review of Molecular Diagnostics·Alessandro RussoChristian Rolfo
Nov 9, 2018·Frontiers in Genetics·Natasha S Clayton, Richard P Grose
Nov 22, 2019·Frontiers in Cell and Developmental Biology·Fei GuoChunlin Shao
Jul 20, 2020·International Journal of Cancer. Journal International Du Cancer·Isabel HeidrichKlaus Pantel
Mar 16, 2019·Journal of Translational Medicine·N García-RomeroA Ayuso-Sacido
Jan 13, 2021·Biomedicines·Patricia Mondelo-MacíaRoberto Díaz-Peña
Nov 22, 2020·Seminars in Cancer Biology·Parvez KhanMohd Wasim Nasser

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