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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
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: Thirty-one patients with advanced sta...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AME Publishing Company
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138977/ https://www.ncbi.nlm.nih.gov/pubmed/32274156 http://dx.doi.org/10.21037/jtd.2019.12.97 |
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author | Zhu, Lucheng Liang, Jiafeng Xia, Bing Xu, Yasi Qian, Ziliang Ma, Shenglin Zhang, Shirong |
author_facet | Zhu, Lucheng Liang, Jiafeng Xia, Bing Xu, Yasi Qian, Ziliang Ma, Shenglin Zhang, Shirong |
author_sort | Zhu, Lucheng |
collection | PubMed |
description | 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: 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: 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(@), ADAMTS18 and CRKL were located. Focal deletions were also found in chr1, 8, 10 and 16, where genes SFTPA1/2, DLC1, PTEN and CDH1 are located. 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. |
format | Online Article Text |
id | pubmed-7138977 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | AME Publishing Company |
record_format | MEDLINE/PubMed |
spelling | pubmed-71389772020-04-09 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 Zhu, Lucheng Liang, Jiafeng Xia, Bing Xu, Yasi Qian, Ziliang Ma, Shenglin Zhang, Shirong J Thorac Dis Original Article 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: 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: 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(@), ADAMTS18 and CRKL were located. Focal deletions were also found in chr1, 8, 10 and 16, where genes SFTPA1/2, DLC1, PTEN and CDH1 are located. 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. AME Publishing Company 2020-03 /pmc/articles/PMC7138977/ /pubmed/32274156 http://dx.doi.org/10.21037/jtd.2019.12.97 Text en 2020 Journal of Thoracic Disease. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Original Article Zhu, Lucheng Liang, Jiafeng Xia, Bing Xu, Yasi Qian, Ziliang Ma, Shenglin Zhang, Shirong 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 |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7138977/ https://www.ncbi.nlm.nih.gov/pubmed/32274156 http://dx.doi.org/10.21037/jtd.2019.12.97 |
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