Application of Next-Generation Sequencing to Realize Principles of Precision Therapy in Management of Cancer Patients
DOI:
https://doi.org/10.15407/exp-oncology.2024.04.295Keywords:
precision oncology, next-generation sequencing, somatic and inherited mutations, liquid biopsyAbstract
All cancers are diseases of the genome, since the cancer cell genome typically consists of 10,000s of passenger alterations, 5—10 biologically relevant alterations, and 1—2 “actionable” alterations. Therefore, somatic mutations in cancer cells can have diagnostic, prognostic, and predictive value. Traditional methods are widely used for testing, such as immunohistochemistry, Sanger sequencing, and allele-specific PCR. However, due to the low throughput, these methods are focused exclusively on testing the most common mutations in target genes. The modern next generation sequencing (NGS) is a technology that enables precision oncology in its current form. ESCAT and ESMO Guidelines defined NGS for routine use in patients with advanced cancers such as non-squamous non-small cell lung cancer, prostate cancer, ovarian cancer, and cholangiocarcinoma. The high sensitivity of the NGS method allows it to be used to search for specific mutations in circulating tumor DNA in blood plasma and other body fluids. NGS testing has evolved from hotspot panels, actionable gene panels, and disease-specific panels to more comprehensive panels. The exome and whole genome sequencing approaches are just beginning to emerge, that is why panel-based testing remains most optimal in oncology practice. NGS is also widely used to identify new and rare mutations in cancer genes and detect inherited cancer mutations.
References
Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229‐263. https://doi.org/10.3322/caac.21834
Zhang S, Xiao X, Yi Y, et al. Tumor initiation and early tumorigenesis: molecular mechanisms and interventional targets. Signal Transduct Target Ther. 2024;9:149. https://doi.org/10.1038/s41392-024-01848-7
Stratton MR, Campbell PJ, Futreal PA. The cancer genome. Nature. 2009;458(7239):719-724. https://doi.org/10.1038/ nature07943
AACR Project GENIE Consortium. AACR Project GENIE: powering precision medicine through an international consortium. Cancer Discov. 2017;7(8):818-831. https://doi.org/10.1158/2159-8290.CD-17-0151
Wenzel C, Herold S, Wermke M, et al. Routine molecular pathology diagnostics in precision oncology. Dtsch Arztebl Int. 2021;118:255-261. https://doi.org/10.3238/arztebl.m2021.0025.
Matos LL, Trufelli DC, de Matos MG, da Silva Pinhal MA. Immunohistochemistry as an important tool in biomarkers detection and clinical practice. Biomark Insights. 2010;5:9-20. https://doi.org/10.4137/bmi.s2185.
IASLC Atlas of ALK and ROS1 Testing in Lung Cancer. Eds.Tsao MS, Hirsch FR, Yatabe Y. 2nd ed. Colorado: Editorial Rx Press, 2016.
Netto GJ, Saad RD, Dysert PA 2nd. Diagnostic molecular pathology: current techniques and clinical applications, part I. Proc (Bayl Univ Med Cent). 2003;16(4):379-383. https://doi.org/10.1080/08998280.2003.11927931
Budhbaware T, Rathored J, Shende S. Molecular methods in cancer diagnostics: a short review. Ann Med.
;56(1):2353893. https://doi.org/10.1080/07853890.2024.2353893
Cervantes A, Adam R, Roselló S, et al. Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34(1):10-32. https://doi.org/10.1016/j.annonc.2022.10.003
IASLC Atlas of Molecular Testing for Targeted Therapy in Lung Cancer. Eds. Sholl LM, Cooper WA, Kerr KM. Inter- national Association for the Study of Lung Cancer, Denver, Co, USA, 2023.
Dong L, Wang W, Li A, et al. Clinical Next Generation Sequencing for precision medicine in cancer. Curr Genomics. 2015;16(4):253-263. https://doi.org/10.2174/1389202915666150511205313
Horak P, Fröhling S, Glimm H. Integrating next-generation sequencing into clinical oncology: strategies, promises and pitfalls. ESMO Open. 2016;1(5):e000094. https://doi.org/10.1136/esmoopen-2016-000094
ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium. Pan-cancer analysis of whole genomes [pub- lished correction appears in Nature. 2023 Feb;614(7948):E39. https://doi.org/ 10.1038/s41586-022-05598-w]. Nature. 2020;578(7793):82-93. https://doi.org/10.1038/s41586-020-1969-6
M. M Li, M. Datto, E. J Duncavage et.al. Standards and guidelines for the interpretation and reporting of sequence variants in cancer. J Mol Diagn. 2017;19(1):4-23. https://doi.org/ 10.1016/j.jmoldx.2016.10.002
Bogdan L, Saleh RR, Avery L, et al. Clinical utility of tumor next-generation sequencing panel testing to inform treat- ment decisions for patients with advanced solid tumors in a tertiary care center. JCO Precis Oncol. 2024;8:e2400092. https://doi.org/10.1200/PO.24.00092
The IASLC Atlas on EGFR Testing in Lung Cancer. Eds. Mok T, Carbone D, Hirsh FR. North Fort Myers: Editorial Rx Press, 2017.
Lu, M.; Zhang, X.; Chu, Q.; et al. Susceptibility genes associated with multiple primary cancers. Cancers. 2023;15:5788. https://doi.org/10.3390/ cancers15245788
S. Kostov, R. Watrowski, Y. Kornovski, et. al. Hereditary gynecologic cancer syndromes — a narrative review. Onco Targets Ther. 2022;15:381-405. https://doi.org/10.2147/OTT.S353054
Mateo J, Chakravarty D, Dienstmann R, et. al. A framework to rank genomic alterations as targets for cancer preci- sion medicine: the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT). Ann Oncol. 2018;29:1895- 1902. https://doi.org/10.1093/annonc/mdy263
Mosele F, Remon J, Mateo J, et al. Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group. Ann Oncol. 2020;31(11):1491- 1505. https://doi.org/10.1016/j.annonc.2020.07.014
Pinto C, Biffoni M, Popoli P, et al. Molecular tests and target therapies in oncology: recommendations from the Italian workshop. Future Oncol. 2021;17(26):3529-3539. https://doi.org/10.2217/fon-2021-0286
Gennari A, André F, Barrios CH, et al. ESMO Clinical Practice Guideline for the diagnosis, staging and treat- ment of patients with metastatic breast cancer. Ann Oncol. 2021;32(12):1475-1495. https://doi.org/10.1016/j.an- nonc.2021.09.019
Gremke N, Rodepeter FR, Teply-Szymanski J, et al. NGS-guided precision oncology in breast cancer and gyne- cological tumors-a retrospective molecular tumor board analysis. Cancers (Basel). 2024;16(8):1561. https://doi. org/10.3390/cancers16081561
Ali-Fehmi R, Krause HB, Morris RT, et al. Analysis of concordance between next-generation sequencing assess- ment of microsatellite instability and immunohistochemistry-mismatch repair from solid tumors. JCO Precis Oncol. 2024;8:e2300648. https://doi.org/10.1200/PO.23.00648
Lau LMS, Khuong-Quang DA, Mayoh C, et al. Precision-guided treatment in high-risk pediatric cancers. Nat Med. 2024;30(7):1913-1922. https://doi.org/10.1038/s41591-024-03044-0.
Barsan V, Paul M, Gorsi H, et al. Clinical impact of next-generation sequencing in pediatric neuro-oncology patients: a single-institutional experience. Cureus. 2019;11(12):e6281. https://doi.org/10.7759/cureus.6281
Church AJ, Corson LB, Kao PC, et al. Molecular profiling identifies targeted therapy opportunities in pediatric solid cancer. Nat Med. 2022;28(8):1581-1589. https://doi.org/10.1038/s41591-022-01856-6
Valenzuela G, Burotto M, Marcelain K, González-Montero J. Liquid biopsy to detect resistance mutations against anti-epidermal growth factor receptor therapy in metastatic colorectal cancer. World J Gastrointest Oncol. 2022;14(9):1654-1664. https://doi.org/10.4251/wjgo.v14.i9.1654
Thenrajan T, Alwarappan S, Wilson J. Molecular diagnosis and cancer prognosis-a concise review. Diagnostics (Basel). 2023;13(4):766. https://doi.org/10.3390/diagnostics13040766
Sahm F, Schrimpf D, Jones DT, et al. Next-generation sequencing in routine brain tumor diagnostics enables an in- tegrated diagnosis and identifies actionable targets. Acta Neuropathol. 2016;131(6):903-910. https://doi.org/10.1007/ s00401-015-1519-8
Bench AJ. The role of molecular genetic analysis within the diagnostic haemato-oncology laboratory. Int J Lab Hematol. 2012;34(1):21-34. https://doi.org/10.1111/j.1751-553X.2011.01364.x
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Experimental Oncology

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.