Cargando…

Prevalence of mutations in common tumour types in Northern England and comparable utility of national and international Trial Finders

PURPOSE: Tumour genomic profiling is of increasing importance in early phase trials to match patients to targeted therapeutics. Mutations vary by demographic group; however, regional differences are not characterised. This was investigated by comparing mutation prevalence for common cancers presenti...

Descripción completa

Detalles Bibliográficos
Autores principales: Rae, S., Plummer, E., Fitzgerald, L., Hogarth, L., Bridgewood, A., Brown-Schofield, L., Graham, J., Haigh, S., McAnulty, C., Drew, Y., Haris, N., Bashir, S., Plummer, R., Greystoke, A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10645649/
https://www.ncbi.nlm.nih.gov/pubmed/37702806
http://dx.doi.org/10.1007/s00432-023-05365-y
_version_ 1785147397775556608
author Rae, S.
Plummer, E.
Fitzgerald, L.
Hogarth, L.
Bridgewood, A.
Brown-Schofield, L.
Graham, J.
Haigh, S.
McAnulty, C.
Drew, Y.
Haris, N.
Bashir, S.
Plummer, R.
Greystoke, A.
author_facet Rae, S.
Plummer, E.
Fitzgerald, L.
Hogarth, L.
Bridgewood, A.
Brown-Schofield, L.
Graham, J.
Haigh, S.
McAnulty, C.
Drew, Y.
Haris, N.
Bashir, S.
Plummer, R.
Greystoke, A.
author_sort Rae, S.
collection PubMed
description PURPOSE: Tumour genomic profiling is of increasing importance in early phase trials to match patients to targeted therapeutics. Mutations vary by demographic group; however, regional differences are not characterised. This was investigated by comparing mutation prevalence for common cancers presenting to Newcastle Experimental Cancer Medicine Centre (ECMC) to The Cancer Genome Atlas (TCGA) and utility of trial matching modalities. METHODS: Detailed clinicogenomic data were obtained for patients presenting September 2017–December 2020. Prevalence of mutations in lung, colorectal, breast and prostate cancer was compared to TCGA GDC Data Portal. Experimental Cancer (EC) Trial Finder utility in matching trials was compared to a Molecular Tumour Board (MTB) and commercial sequencing reports. RESULTS: Of 311 patients with advanced cancer, this consisted of lung (n = 131, 42.1%), colorectal (n = 44, 14.1%), breast (n = 36, 11.6%) and prostate (n = 18, 5.6%). More than one mutation was identified in the majority (n = 260, 84%). Significant prevalence differences compared to TCGA were identified, including a high prevalence of EGFR in lung (P = 0.001); RB1 in breast (P = 0.0002); and multiple mutations in prostate cancer. EC Trial Finder demonstrated significantly different utility than sequencing reports in identifying trials (P = 0.007). CONCLUSIONS: Regional differences in mutations may exist with advanced stage accounting for prevalence of specific mutations. A national Trial Finder shows utility in finding targeted trials whilst commercial sequencing reports may over-report ‘actionable’ mutations. Understanding local prevalence and trial availability could increase enrolment onto matched early phase trials. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00432-023-05365-y.
format Online
Article
Text
id pubmed-10645649
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Springer Berlin Heidelberg
record_format MEDLINE/PubMed
spelling pubmed-106456492023-11-14 Prevalence of mutations in common tumour types in Northern England and comparable utility of national and international Trial Finders Rae, S. Plummer, E. Fitzgerald, L. Hogarth, L. Bridgewood, A. Brown-Schofield, L. Graham, J. Haigh, S. McAnulty, C. Drew, Y. Haris, N. Bashir, S. Plummer, R. Greystoke, A. J Cancer Res Clin Oncol Research PURPOSE: Tumour genomic profiling is of increasing importance in early phase trials to match patients to targeted therapeutics. Mutations vary by demographic group; however, regional differences are not characterised. This was investigated by comparing mutation prevalence for common cancers presenting to Newcastle Experimental Cancer Medicine Centre (ECMC) to The Cancer Genome Atlas (TCGA) and utility of trial matching modalities. METHODS: Detailed clinicogenomic data were obtained for patients presenting September 2017–December 2020. Prevalence of mutations in lung, colorectal, breast and prostate cancer was compared to TCGA GDC Data Portal. Experimental Cancer (EC) Trial Finder utility in matching trials was compared to a Molecular Tumour Board (MTB) and commercial sequencing reports. RESULTS: Of 311 patients with advanced cancer, this consisted of lung (n = 131, 42.1%), colorectal (n = 44, 14.1%), breast (n = 36, 11.6%) and prostate (n = 18, 5.6%). More than one mutation was identified in the majority (n = 260, 84%). Significant prevalence differences compared to TCGA were identified, including a high prevalence of EGFR in lung (P = 0.001); RB1 in breast (P = 0.0002); and multiple mutations in prostate cancer. EC Trial Finder demonstrated significantly different utility than sequencing reports in identifying trials (P = 0.007). CONCLUSIONS: Regional differences in mutations may exist with advanced stage accounting for prevalence of specific mutations. A national Trial Finder shows utility in finding targeted trials whilst commercial sequencing reports may over-report ‘actionable’ mutations. Understanding local prevalence and trial availability could increase enrolment onto matched early phase trials. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00432-023-05365-y. Springer Berlin Heidelberg 2023-09-13 2023 /pmc/articles/PMC10645649/ /pubmed/37702806 http://dx.doi.org/10.1007/s00432-023-05365-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research
Rae, S.
Plummer, E.
Fitzgerald, L.
Hogarth, L.
Bridgewood, A.
Brown-Schofield, L.
Graham, J.
Haigh, S.
McAnulty, C.
Drew, Y.
Haris, N.
Bashir, S.
Plummer, R.
Greystoke, A.
Prevalence of mutations in common tumour types in Northern England and comparable utility of national and international Trial Finders
title Prevalence of mutations in common tumour types in Northern England and comparable utility of national and international Trial Finders
title_full Prevalence of mutations in common tumour types in Northern England and comparable utility of national and international Trial Finders
title_fullStr Prevalence of mutations in common tumour types in Northern England and comparable utility of national and international Trial Finders
title_full_unstemmed Prevalence of mutations in common tumour types in Northern England and comparable utility of national and international Trial Finders
title_short Prevalence of mutations in common tumour types in Northern England and comparable utility of national and international Trial Finders
title_sort prevalence of mutations in common tumour types in northern england and comparable utility of national and international trial finders
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10645649/
https://www.ncbi.nlm.nih.gov/pubmed/37702806
http://dx.doi.org/10.1007/s00432-023-05365-y
work_keys_str_mv AT raes prevalenceofmutationsincommontumourtypesinnorthernenglandandcomparableutilityofnationalandinternationaltrialfinders
AT plummere prevalenceofmutationsincommontumourtypesinnorthernenglandandcomparableutilityofnationalandinternationaltrialfinders
AT fitzgeraldl prevalenceofmutationsincommontumourtypesinnorthernenglandandcomparableutilityofnationalandinternationaltrialfinders
AT hogarthl prevalenceofmutationsincommontumourtypesinnorthernenglandandcomparableutilityofnationalandinternationaltrialfinders
AT bridgewooda prevalenceofmutationsincommontumourtypesinnorthernenglandandcomparableutilityofnationalandinternationaltrialfinders
AT brownschofieldl prevalenceofmutationsincommontumourtypesinnorthernenglandandcomparableutilityofnationalandinternationaltrialfinders
AT grahamj prevalenceofmutationsincommontumourtypesinnorthernenglandandcomparableutilityofnationalandinternationaltrialfinders
AT haighs prevalenceofmutationsincommontumourtypesinnorthernenglandandcomparableutilityofnationalandinternationaltrialfinders
AT mcanultyc prevalenceofmutationsincommontumourtypesinnorthernenglandandcomparableutilityofnationalandinternationaltrialfinders
AT drewy prevalenceofmutationsincommontumourtypesinnorthernenglandandcomparableutilityofnationalandinternationaltrialfinders
AT harisn prevalenceofmutationsincommontumourtypesinnorthernenglandandcomparableutilityofnationalandinternationaltrialfinders
AT bashirs prevalenceofmutationsincommontumourtypesinnorthernenglandandcomparableutilityofnationalandinternationaltrialfinders
AT plummerr prevalenceofmutationsincommontumourtypesinnorthernenglandandcomparableutilityofnationalandinternationaltrialfinders
AT greystokea prevalenceofmutationsincommontumourtypesinnorthernenglandandcomparableutilityofnationalandinternationaltrialfinders