Cargando…

Correlation of treatment outcome in sanger/RT-qPCR KIT/PDGFRA wild-type metastatic gastrointestinal stromal tumors with next-generation sequencing results: A single-center report

In patients with gastrointestinal stromal tumors (GIST), it has become mandatory to determine the driver mutation in order to predict the response to standard treatment with tyrosine kinase inhibitors (TKI). A total of 10–15% of all GIST lack activating mutations in KIT proto-oncogene, receptor tyro...

Descripción completa

Detalles Bibliográficos
Autores principales: Unk, Mojca, Bombač, Alenka, Jezeršek Novaković, Barbara, Stegel, Vida, šetrajčič Dragoš, Vita, Blatnik, Olga, Klančar, Gašper, Novaković, Srdjan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9351002/
https://www.ncbi.nlm.nih.gov/pubmed/35904169
http://dx.doi.org/10.3892/or.2022.8382
_version_ 1784762343117291520
author Unk, Mojca
Bombač, Alenka
Jezeršek Novaković, Barbara
Stegel, Vida
šetrajčič Dragoš, Vita
Blatnik, Olga
Klančar, Gašper
Novaković, Srdjan
author_facet Unk, Mojca
Bombač, Alenka
Jezeršek Novaković, Barbara
Stegel, Vida
šetrajčič Dragoš, Vita
Blatnik, Olga
Klančar, Gašper
Novaković, Srdjan
author_sort Unk, Mojca
collection PubMed
description In patients with gastrointestinal stromal tumors (GIST), it has become mandatory to determine the driver mutation in order to predict the response to standard treatment with tyrosine kinase inhibitors (TKI). A total of 10–15% of all GIST lack activating mutations in KIT proto-oncogene, receptor tyrosine kinase (KIT)/platelet-derived growth factor receptor alpha (PDGFRA) and have been classified as KIT/PDGFRA wild-type (WT) GIST. They are characterized by poor response to TKI. From a group of 119 metastatic GIST patients, 17 patients with KIT/PDGFRA/BRAF WT GIST as determined by reverse transcription-quantitative (RT-q) PCR and Sanger sequencing were profiled by a targeted next-generation sequencing (NGS) approach and their treatment outcome was assessed. In the present study, 41.2% of patients as KIT/PDGFRA/BRAF WT GIST examined with RT-qPCR and Sanger sequencing were confirmed to be carriers of pathogenic KIT/PDGFRA mutations by NGS and were responsive to TKI. The percentage of genuinely KIT/PDGFRA WT GIST in the present study thereby dropped from the initial 14.3% detected with the RT-qPCR and Sanger sequencing to 7.6% after NGS. Their outcome was universally poor. The reliability of RT-qPCR and direct Sanger sequencing results in this setting is therefore insufficient and it is recommended that NGS becomes a requirement for treatment decision at least in KIT/PDGFRA/BRAF WT GIST as determined by RT-qPCR and Sanger sequencing.
format Online
Article
Text
id pubmed-9351002
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher D.A. Spandidos
record_format MEDLINE/PubMed
spelling pubmed-93510022022-08-09 Correlation of treatment outcome in sanger/RT-qPCR KIT/PDGFRA wild-type metastatic gastrointestinal stromal tumors with next-generation sequencing results: A single-center report Unk, Mojca Bombač, Alenka Jezeršek Novaković, Barbara Stegel, Vida šetrajčič Dragoš, Vita Blatnik, Olga Klančar, Gašper Novaković, Srdjan Oncol Rep Articles In patients with gastrointestinal stromal tumors (GIST), it has become mandatory to determine the driver mutation in order to predict the response to standard treatment with tyrosine kinase inhibitors (TKI). A total of 10–15% of all GIST lack activating mutations in KIT proto-oncogene, receptor tyrosine kinase (KIT)/platelet-derived growth factor receptor alpha (PDGFRA) and have been classified as KIT/PDGFRA wild-type (WT) GIST. They are characterized by poor response to TKI. From a group of 119 metastatic GIST patients, 17 patients with KIT/PDGFRA/BRAF WT GIST as determined by reverse transcription-quantitative (RT-q) PCR and Sanger sequencing were profiled by a targeted next-generation sequencing (NGS) approach and their treatment outcome was assessed. In the present study, 41.2% of patients as KIT/PDGFRA/BRAF WT GIST examined with RT-qPCR and Sanger sequencing were confirmed to be carriers of pathogenic KIT/PDGFRA mutations by NGS and were responsive to TKI. The percentage of genuinely KIT/PDGFRA WT GIST in the present study thereby dropped from the initial 14.3% detected with the RT-qPCR and Sanger sequencing to 7.6% after NGS. Their outcome was universally poor. The reliability of RT-qPCR and direct Sanger sequencing results in this setting is therefore insufficient and it is recommended that NGS becomes a requirement for treatment decision at least in KIT/PDGFRA/BRAF WT GIST as determined by RT-qPCR and Sanger sequencing. D.A. Spandidos 2022-07-28 /pmc/articles/PMC9351002/ /pubmed/35904169 http://dx.doi.org/10.3892/or.2022.8382 Text en Copyright: © Unk et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Unk, Mojca
Bombač, Alenka
Jezeršek Novaković, Barbara
Stegel, Vida
šetrajčič Dragoš, Vita
Blatnik, Olga
Klančar, Gašper
Novaković, Srdjan
Correlation of treatment outcome in sanger/RT-qPCR KIT/PDGFRA wild-type metastatic gastrointestinal stromal tumors with next-generation sequencing results: A single-center report
title Correlation of treatment outcome in sanger/RT-qPCR KIT/PDGFRA wild-type metastatic gastrointestinal stromal tumors with next-generation sequencing results: A single-center report
title_full Correlation of treatment outcome in sanger/RT-qPCR KIT/PDGFRA wild-type metastatic gastrointestinal stromal tumors with next-generation sequencing results: A single-center report
title_fullStr Correlation of treatment outcome in sanger/RT-qPCR KIT/PDGFRA wild-type metastatic gastrointestinal stromal tumors with next-generation sequencing results: A single-center report
title_full_unstemmed Correlation of treatment outcome in sanger/RT-qPCR KIT/PDGFRA wild-type metastatic gastrointestinal stromal tumors with next-generation sequencing results: A single-center report
title_short Correlation of treatment outcome in sanger/RT-qPCR KIT/PDGFRA wild-type metastatic gastrointestinal stromal tumors with next-generation sequencing results: A single-center report
title_sort correlation of treatment outcome in sanger/rt-qpcr kit/pdgfra wild-type metastatic gastrointestinal stromal tumors with next-generation sequencing results: a single-center report
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9351002/
https://www.ncbi.nlm.nih.gov/pubmed/35904169
http://dx.doi.org/10.3892/or.2022.8382
work_keys_str_mv AT unkmojca correlationoftreatmentoutcomeinsangerrtqpcrkitpdgfrawildtypemetastaticgastrointestinalstromaltumorswithnextgenerationsequencingresultsasinglecenterreport
AT bombacalenka correlationoftreatmentoutcomeinsangerrtqpcrkitpdgfrawildtypemetastaticgastrointestinalstromaltumorswithnextgenerationsequencingresultsasinglecenterreport
AT jezerseknovakovicbarbara correlationoftreatmentoutcomeinsangerrtqpcrkitpdgfrawildtypemetastaticgastrointestinalstromaltumorswithnextgenerationsequencingresultsasinglecenterreport
AT stegelvida correlationoftreatmentoutcomeinsangerrtqpcrkitpdgfrawildtypemetastaticgastrointestinalstromaltumorswithnextgenerationsequencingresultsasinglecenterreport
AT setrajcicdragosvita correlationoftreatmentoutcomeinsangerrtqpcrkitpdgfrawildtypemetastaticgastrointestinalstromaltumorswithnextgenerationsequencingresultsasinglecenterreport
AT blatnikolga correlationoftreatmentoutcomeinsangerrtqpcrkitpdgfrawildtypemetastaticgastrointestinalstromaltumorswithnextgenerationsequencingresultsasinglecenterreport
AT klancargasper correlationoftreatmentoutcomeinsangerrtqpcrkitpdgfrawildtypemetastaticgastrointestinalstromaltumorswithnextgenerationsequencingresultsasinglecenterreport
AT novakovicsrdjan correlationoftreatmentoutcomeinsangerrtqpcrkitpdgfrawildtypemetastaticgastrointestinalstromaltumorswithnextgenerationsequencingresultsasinglecenterreport