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Integrative Genomic Tests in Clinical Oncology

Many clinical decisions in oncology practice rely on the presence or absence of an alteration in a single genetic locus, be it a pathogenic variant in a hereditary cancer gene or activating mutation in a drug target. In addition, there are integrative tests that produce continuous variables and eval...

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Autores principales: Imyanitov, Evgeny, Sokolenko, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9656402/
https://www.ncbi.nlm.nih.gov/pubmed/36361916
http://dx.doi.org/10.3390/ijms232113129
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author Imyanitov, Evgeny
Sokolenko, Anna
author_facet Imyanitov, Evgeny
Sokolenko, Anna
author_sort Imyanitov, Evgeny
collection PubMed
description Many clinical decisions in oncology practice rely on the presence or absence of an alteration in a single genetic locus, be it a pathogenic variant in a hereditary cancer gene or activating mutation in a drug target. In addition, there are integrative tests that produce continuous variables and evaluate complex characteristics of the entire tumor genome. Microsatellite instability (MSI) analysis identifies tumors with the accumulation of mutations in short repetitive nucleotide sequences. This procedure is utilized in Lynch syndrome diagnostic pipelines and for the selection of patients for immunotherapy. MSI analysis is well-established for colorectal malignancies, but its applications in other cancer types lack standardization and require additional research. Homologous repair deficiency (HRD) indicates tumor sensitivity to PARP inhibitors and some cytotoxic drugs. HRD-related “genomic scars” are manifested by a characteristic pattern of allelic imbalances, accumulation of deletions with flanking homology, and specific mutation signatures. The detection of the genetic consequences of HRD is particularly sophisticated and expensive, as it involves either whole genome sequencing (WGS) or the utilization of large next-generation sequencing (NGS) panels. Tumor mutation burden (TMB) can be determined by whole exome sequencing (WES) or middle-throughput NGS multigene testing. Although TMB is regarded as an agnostic indicator of tumor sensitivity to immunotherapy, the clinical utility of this test is proven only for a few cancer types.
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spelling pubmed-96564022022-11-15 Integrative Genomic Tests in Clinical Oncology Imyanitov, Evgeny Sokolenko, Anna Int J Mol Sci Review Many clinical decisions in oncology practice rely on the presence or absence of an alteration in a single genetic locus, be it a pathogenic variant in a hereditary cancer gene or activating mutation in a drug target. In addition, there are integrative tests that produce continuous variables and evaluate complex characteristics of the entire tumor genome. Microsatellite instability (MSI) analysis identifies tumors with the accumulation of mutations in short repetitive nucleotide sequences. This procedure is utilized in Lynch syndrome diagnostic pipelines and for the selection of patients for immunotherapy. MSI analysis is well-established for colorectal malignancies, but its applications in other cancer types lack standardization and require additional research. Homologous repair deficiency (HRD) indicates tumor sensitivity to PARP inhibitors and some cytotoxic drugs. HRD-related “genomic scars” are manifested by a characteristic pattern of allelic imbalances, accumulation of deletions with flanking homology, and specific mutation signatures. The detection of the genetic consequences of HRD is particularly sophisticated and expensive, as it involves either whole genome sequencing (WGS) or the utilization of large next-generation sequencing (NGS) panels. Tumor mutation burden (TMB) can be determined by whole exome sequencing (WES) or middle-throughput NGS multigene testing. Although TMB is regarded as an agnostic indicator of tumor sensitivity to immunotherapy, the clinical utility of this test is proven only for a few cancer types. MDPI 2022-10-28 /pmc/articles/PMC9656402/ /pubmed/36361916 http://dx.doi.org/10.3390/ijms232113129 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Imyanitov, Evgeny
Sokolenko, Anna
Integrative Genomic Tests in Clinical Oncology
title Integrative Genomic Tests in Clinical Oncology
title_full Integrative Genomic Tests in Clinical Oncology
title_fullStr Integrative Genomic Tests in Clinical Oncology
title_full_unstemmed Integrative Genomic Tests in Clinical Oncology
title_short Integrative Genomic Tests in Clinical Oncology
title_sort integrative genomic tests in clinical oncology
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9656402/
https://www.ncbi.nlm.nih.gov/pubmed/36361916
http://dx.doi.org/10.3390/ijms232113129
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