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Frequency, underdiagnosis, and heterogeneity of epidermal growth factor receptor exon 20 insertion mutations using real‐world genomic datasets
Epidermal growth factor receptor (EGFR) exon 20 insertion mutations (ex20ins) account for ≤ 12% of all EGFR‐mutant nonsmall cell lung cancers. We analysed real‐world datasets to determine the frequency of ex20ins variants, and the ability of polymerase chain reaction (PCR) and next‐generation sequen...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9892822/ https://www.ncbi.nlm.nih.gov/pubmed/36269676 http://dx.doi.org/10.1002/1878-0261.13327 |
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author | Viteri, Santiago Minchom, Anna Bazhenova, Lyudmila Ou, Sai‐Hong Ignatius Bauml, Joshua M. Shell, Scott A. Schaffer, Michael Gu, Junchen Rose, Jennifer B. Curtin, Joshua C. Mahadevia, Parthiv Girard, Nicolas |
author_facet | Viteri, Santiago Minchom, Anna Bazhenova, Lyudmila Ou, Sai‐Hong Ignatius Bauml, Joshua M. Shell, Scott A. Schaffer, Michael Gu, Junchen Rose, Jennifer B. Curtin, Joshua C. Mahadevia, Parthiv Girard, Nicolas |
author_sort | Viteri, Santiago |
collection | PubMed |
description | Epidermal growth factor receptor (EGFR) exon 20 insertion mutations (ex20ins) account for ≤ 12% of all EGFR‐mutant nonsmall cell lung cancers. We analysed real‐world datasets to determine the frequency of ex20ins variants, and the ability of polymerase chain reaction (PCR) and next‐generation sequencing (NGS) to identify them. Three real‐world United States NGS databases were used: GENIE, FoundationInsights, and GuardantINFORM. Mutation profiles consistent with in‐frame EGFR ex20ins were summarized. GENIE, FoundationInsights, and GuardantINFORM datasets identified 180, 627, and 627 patients with EGFR ex20ins respectively. The most frequent insertion region of exon 20 was the near loop (~ 70%), followed by the far loop (~ 30%) and the helical (~ 3–6%) regions. GENIE, FoundationInsights, and GuardantINFORM datasets identified 41, 102, and 96 unique variants respectively. An analysis of variants projected that ~ 50% of EGFR ex20ins identified by NGS would have been missed by PCR‐based assays. Given the breadth of EGFR ex20ins identified in the real‐world US datasets, the ability of PCR to identify these mutations is limited. NGS platforms are more appropriate to identify patients likely to benefit from EGFR ex20ins‐targeted therapies. |
format | Online Article Text |
id | pubmed-9892822 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-98928222023-02-06 Frequency, underdiagnosis, and heterogeneity of epidermal growth factor receptor exon 20 insertion mutations using real‐world genomic datasets Viteri, Santiago Minchom, Anna Bazhenova, Lyudmila Ou, Sai‐Hong Ignatius Bauml, Joshua M. Shell, Scott A. Schaffer, Michael Gu, Junchen Rose, Jennifer B. Curtin, Joshua C. Mahadevia, Parthiv Girard, Nicolas Mol Oncol Short Report Epidermal growth factor receptor (EGFR) exon 20 insertion mutations (ex20ins) account for ≤ 12% of all EGFR‐mutant nonsmall cell lung cancers. We analysed real‐world datasets to determine the frequency of ex20ins variants, and the ability of polymerase chain reaction (PCR) and next‐generation sequencing (NGS) to identify them. Three real‐world United States NGS databases were used: GENIE, FoundationInsights, and GuardantINFORM. Mutation profiles consistent with in‐frame EGFR ex20ins were summarized. GENIE, FoundationInsights, and GuardantINFORM datasets identified 180, 627, and 627 patients with EGFR ex20ins respectively. The most frequent insertion region of exon 20 was the near loop (~ 70%), followed by the far loop (~ 30%) and the helical (~ 3–6%) regions. GENIE, FoundationInsights, and GuardantINFORM datasets identified 41, 102, and 96 unique variants respectively. An analysis of variants projected that ~ 50% of EGFR ex20ins identified by NGS would have been missed by PCR‐based assays. Given the breadth of EGFR ex20ins identified in the real‐world US datasets, the ability of PCR to identify these mutations is limited. NGS platforms are more appropriate to identify patients likely to benefit from EGFR ex20ins‐targeted therapies. John Wiley and Sons Inc. 2022-11-28 /pmc/articles/PMC9892822/ /pubmed/36269676 http://dx.doi.org/10.1002/1878-0261.13327 Text en © 2022 Janssen Global Services, LLC. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Short Report Viteri, Santiago Minchom, Anna Bazhenova, Lyudmila Ou, Sai‐Hong Ignatius Bauml, Joshua M. Shell, Scott A. Schaffer, Michael Gu, Junchen Rose, Jennifer B. Curtin, Joshua C. Mahadevia, Parthiv Girard, Nicolas Frequency, underdiagnosis, and heterogeneity of epidermal growth factor receptor exon 20 insertion mutations using real‐world genomic datasets |
title | Frequency, underdiagnosis, and heterogeneity of epidermal growth factor receptor exon 20 insertion mutations using real‐world genomic datasets |
title_full | Frequency, underdiagnosis, and heterogeneity of epidermal growth factor receptor exon 20 insertion mutations using real‐world genomic datasets |
title_fullStr | Frequency, underdiagnosis, and heterogeneity of epidermal growth factor receptor exon 20 insertion mutations using real‐world genomic datasets |
title_full_unstemmed | Frequency, underdiagnosis, and heterogeneity of epidermal growth factor receptor exon 20 insertion mutations using real‐world genomic datasets |
title_short | Frequency, underdiagnosis, and heterogeneity of epidermal growth factor receptor exon 20 insertion mutations using real‐world genomic datasets |
title_sort | frequency, underdiagnosis, and heterogeneity of epidermal growth factor receptor exon 20 insertion mutations using real‐world genomic datasets |
topic | Short Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9892822/ https://www.ncbi.nlm.nih.gov/pubmed/36269676 http://dx.doi.org/10.1002/1878-0261.13327 |
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