Identification of somatic copy number variations in plasma cell free DNA correlating with intrinsic resistances to EGFR targeted therapy in T790M negative non-small cell lung cancer.
Copy number variations (CNV)
T790M negative
intrinsic resistances
non-small cell lung cancer (NSCLC)
plasma cell free DNA (cfDNA)
Journal
Journal of thoracic disease
ISSN: 2072-1439
Titre abrégé: J Thorac Dis
Pays: China
ID NLM: 101533916
Informations de publication
Date de publication:
Mar 2020
Mar 2020
Historique:
entrez:
11
4
2020
pubmed:
11
4
2020
medline:
11
4
2020
Statut:
ppublish
Résumé
About 20-30% EGFR-mutant non-small lung cancer show intrinsic resistance to EGFR targeted therapies. Compared to T790M positive in acquired resistance patients, little is known about EGFR-TKI intrinsic resistance for T790M negative patients. Thirty-one patients with advanced stage lung cancer, including 18 patients with intrinsic resistance (PFS <6 months) and 13 patients with acquired resistance (PFS >36 months) but are negative for plasma T790M were recruited in the study. Plasma cell free DNA was profiled by low coverage whole genome sequencing with median genome coverage of 1.86X by Illumina X10. Sequencing coverage across chromosomes was summarized by samtools, and normalized by segmentation analysis as provided by R package 'DNACopy'. The most frequent chromosomal changes were found on chr7, chr1 and chr8. Among them, chr7p gains were found in 12 (66.7%) intrinsic resistance and 4 (30.7%) acquired resistance patients. The gene EGFR was found located on the focal amplification peak of chr7p. The performance of 7p gain to predict intrinsic resistance reaches AUC =0.902. Similarly, focal amplifications were also found on chromosome 5, 16 and 22, where tumor related gene PCDHA The results suggest cell free DNA copy number might be a useful peripheral blood tumor biomarker for predicting intrinsic resistance of EGFR targeted therapy and prognosis.
Sections du résumé
BACKGROUND
BACKGROUND
About 20-30% EGFR-mutant non-small lung cancer show intrinsic resistance to EGFR targeted therapies. Compared to T790M positive in acquired resistance patients, little is known about EGFR-TKI intrinsic resistance for T790M negative patients.
METHODS
METHODS
Thirty-one patients with advanced stage lung cancer, including 18 patients with intrinsic resistance (PFS <6 months) and 13 patients with acquired resistance (PFS >36 months) but are negative for plasma T790M were recruited in the study. Plasma cell free DNA was profiled by low coverage whole genome sequencing with median genome coverage of 1.86X by Illumina X10. Sequencing coverage across chromosomes was summarized by samtools, and normalized by segmentation analysis as provided by R package 'DNACopy'.
RESULTS
RESULTS
The most frequent chromosomal changes were found on chr7, chr1 and chr8. Among them, chr7p gains were found in 12 (66.7%) intrinsic resistance and 4 (30.7%) acquired resistance patients. The gene EGFR was found located on the focal amplification peak of chr7p. The performance of 7p gain to predict intrinsic resistance reaches AUC =0.902. Similarly, focal amplifications were also found on chromosome 5, 16 and 22, where tumor related gene PCDHA
CONCLUSIONS
CONCLUSIONS
The results suggest cell free DNA copy number might be a useful peripheral blood tumor biomarker for predicting intrinsic resistance of EGFR targeted therapy and prognosis.
Identifiants
pubmed: 32274156
doi: 10.21037/jtd.2019.12.97
pii: jtd-12-03-883
pmc: PMC7138977
doi:
Types de publication
Journal Article
Langues
eng
Pagination
883-892Informations de copyright
2020 Journal of Thoracic Disease. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of Interest: The authors have no conflicts of interest to declare.
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