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An innovative diagnostic strategy for the detection of rare molecular targets to select cancer patients for tumor-agnostic treatments
Targeted therapies are playing an increasing role in oncology. Among them, particular attention is nowadays reserved to histology-agnostic treatments. Rare molecular alterations affecting different neoplastic forms, such as Microsatellite Instability (MSI), Neurotropic Tyrosine Receptor Kinase (NTRK...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6916754/ https://www.ncbi.nlm.nih.gov/pubmed/31857850 http://dx.doi.org/10.18632/oncotarget.27343 |
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author | Marchetti, Antonio Di Lorito, Alessia Felicioni, Lara Buttitta, Fiamma |
author_facet | Marchetti, Antonio Di Lorito, Alessia Felicioni, Lara Buttitta, Fiamma |
author_sort | Marchetti, Antonio |
collection | PubMed |
description | Targeted therapies are playing an increasing role in oncology. Among them, particular attention is nowadays reserved to histology-agnostic treatments. Rare molecular alterations affecting different neoplastic forms, such as Microsatellite Instability (MSI), Neurotropic Tyrosine Receptor Kinase (NTRK) gene fusions, etc., can allow efficient treatments, irrespective of the histologic type. Developing an effective testing strategy for the detection of rare molecular alterations is challenging. We report an innovative diagnostic strategy for a rapid and economically affordable detection of this uncommon targets. Malignant tumor samples are selected at the time of histopathological diagnosis and further processed for simultaneous analysis of multiple samples on Tissue Micro Arrays (TMAs) and Tissue Slice Arrays (TSAs). The TSA approach was specifically designed for large scale screening of small biopsies. TMA sections and TSA were first screened by immunohistochemistry (IHC) for the expression of mismatch repair and TRK proteins. Positive cases were subjected to confirmation tests (fragment analysis/FISH/NGS). In a series of 1865 malignant tumors, 48 (2.6%) MSI cases and 6 (0.3%) NTRK fusion cases were detected in 9 and 4 different tumor forms, respectively. On average, the TMA/TSA screening approach enabled IHC analysis of about 20 patients simultaneously with significant saving of time and costs. In addition, we have shown that multiplex IHC can further increment the throughput. A detailed procedure for application of this diagnostic approach in clinical practice is reported. The strategy described may allow an efficient and sustainable selection of tumors carrying rare molecular targets, not to leave behind patients for effective agnostic treatments. |
format | Online Article Text |
id | pubmed-6916754 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-69167542019-12-19 An innovative diagnostic strategy for the detection of rare molecular targets to select cancer patients for tumor-agnostic treatments Marchetti, Antonio Di Lorito, Alessia Felicioni, Lara Buttitta, Fiamma Oncotarget Research Paper Targeted therapies are playing an increasing role in oncology. Among them, particular attention is nowadays reserved to histology-agnostic treatments. Rare molecular alterations affecting different neoplastic forms, such as Microsatellite Instability (MSI), Neurotropic Tyrosine Receptor Kinase (NTRK) gene fusions, etc., can allow efficient treatments, irrespective of the histologic type. Developing an effective testing strategy for the detection of rare molecular alterations is challenging. We report an innovative diagnostic strategy for a rapid and economically affordable detection of this uncommon targets. Malignant tumor samples are selected at the time of histopathological diagnosis and further processed for simultaneous analysis of multiple samples on Tissue Micro Arrays (TMAs) and Tissue Slice Arrays (TSAs). The TSA approach was specifically designed for large scale screening of small biopsies. TMA sections and TSA were first screened by immunohistochemistry (IHC) for the expression of mismatch repair and TRK proteins. Positive cases were subjected to confirmation tests (fragment analysis/FISH/NGS). In a series of 1865 malignant tumors, 48 (2.6%) MSI cases and 6 (0.3%) NTRK fusion cases were detected in 9 and 4 different tumor forms, respectively. On average, the TMA/TSA screening approach enabled IHC analysis of about 20 patients simultaneously with significant saving of time and costs. In addition, we have shown that multiplex IHC can further increment the throughput. A detailed procedure for application of this diagnostic approach in clinical practice is reported. The strategy described may allow an efficient and sustainable selection of tumors carrying rare molecular targets, not to leave behind patients for effective agnostic treatments. Impact Journals LLC 2019-12-10 /pmc/articles/PMC6916754/ /pubmed/31857850 http://dx.doi.org/10.18632/oncotarget.27343 Text en Copyright: Marchetti et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Marchetti, Antonio Di Lorito, Alessia Felicioni, Lara Buttitta, Fiamma An innovative diagnostic strategy for the detection of rare molecular targets to select cancer patients for tumor-agnostic treatments |
title | An innovative diagnostic strategy for the detection of rare molecular targets to select cancer patients for tumor-agnostic treatments |
title_full | An innovative diagnostic strategy for the detection of rare molecular targets to select cancer patients for tumor-agnostic treatments |
title_fullStr | An innovative diagnostic strategy for the detection of rare molecular targets to select cancer patients for tumor-agnostic treatments |
title_full_unstemmed | An innovative diagnostic strategy for the detection of rare molecular targets to select cancer patients for tumor-agnostic treatments |
title_short | An innovative diagnostic strategy for the detection of rare molecular targets to select cancer patients for tumor-agnostic treatments |
title_sort | innovative diagnostic strategy for the detection of rare molecular targets to select cancer patients for tumor-agnostic treatments |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6916754/ https://www.ncbi.nlm.nih.gov/pubmed/31857850 http://dx.doi.org/10.18632/oncotarget.27343 |
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