Clinical Application of a Cancer Genomic Profiling Assay to Guide Precision Medicine Decisions

Overview

Journal Per Med

Specialties General Medicine
Genetics

Date 2017 Sep 12

PMID 28890729

Citations 17

Authors

Cheryl Eifert

Angeliki Pantazi

Ruobai Sun

Jia Xu

Pablo Cingolani

Joerg Heyer

Meaghan Russell

Maria Lvova

Jennifer Ring

Julie Y Tse

Stephen Lyle

Alexei Protopopov

Affiliations

Soon will be listed here.

Abstract

Aim: Develop and apply a comprehensive and accurate next-generation sequencing based assay to help clinicians to match oncology patients to therapies.

Materials & Methods: The performance of the CANCERPLEX assay was assessed using DNA from well-characterized routine clinical formalin-fixed paraffin-embedded (FFPE) specimens and cell lines.

Results: The maximum sensitivity of the assay is 99.5% and its accuracy is virtually 100% for detecting somatic alterations with an allele fraction of as low as 10%. Clinically actionable variants were identified in 93% of patients (930 of 1000) who underwent testing.

Conclusion: The test's capacity to determine all of the critical genetic changes, tumor mutation burden, microsatellite instability status and viral associations has important ramifications on clinical decision support strategies, including identification of patients who are likely to benefit from immune checkpoint blockage therapies.

Citing Articles

Tumor-Agnostic Therapy-The Final Step Forward in the Cure for Human Neoplasms?.

El-Sayed M, Bianco J, Li Y, Fabian Z Cells. 2024; 13(12.

PMID: 38920700 PMC: 11201516. DOI: 10.3390/cells13121071.

Clinical application of targeted tumour sequencing tests for detecting ERBB2 amplification and optimizing anti-HER2 therapy in gastric cancer.

Ichikawa H, Usui K, Aizawa M, Shimada Y, Muneoka Y, Kano Y BMC Cancer. 2024; 24(1):719.

PMID: 38862927 PMC: 11167924. DOI: 10.1186/s12885-024-12482-5.

Multi-omics analyses of choroid plexus carcinoma cell lines reveal potential targetable pathways and alterations.

Hesham D, On J, Alshahaby N, Amer N, Magdeldin S, Okada M J Neurooncol. 2024; 166(1):27-38.

PMID: 38190092 DOI: 10.1007/s11060-023-04484-3.

Genomic characterization between HER2-positive and negative gastric cancer patients in a prospective trial.

Hu Q, Oki E, Yamada T, Kashiwada T, Sonoda H, Kataoka M Cancer Med. 2023; 12(15):16649-16660.

PMID: 37325934 PMC: 10469643. DOI: 10.1002/cam4.6269.

Genomic and transcriptomic profiling indicates the prognosis significance of mutational signature for TMB-high subtype in Chinese patients with gastric cancer.

Cheng Y, Bu D, Zhang Q, Sun R, Lyle S, Zhao G J Adv Res. 2022; 51:121-134.

PMID: 36351537 PMC: 10491970. DOI: 10.1016/j.jare.2022.10.019.

References

Tsuta K, Kohno T, Yoshida A, Shimada Y, Asamura H, Furuta K . RET-rearranged non-small-cell lung carcinoma: a clinicopathological and molecular analysis. Br J Cancer. 2014; 110(6):1571-8. PMC: 3960615. DOI: 10.1038/bjc.2014.36. View

Bergethon K, Shaw A, Ou S, Katayama R, Lovly C, McDonald N . ROS1 rearrangements define a unique molecular class of lung cancers. J Clin Oncol. 2012; 30(8):863-70. PMC: 3295572. DOI: 10.1200/JCO.2011.35.6345. View

Bilgin Sonay T, Koletou M, Wagner A . A survey of tandem repeat instabilities and associated gene expression changes in 35 colorectal cancers. BMC Genomics. 2015; 16:702. PMC: 4574073. DOI: 10.1186/s12864-015-1902-9. View

Ingle J, Suman V, Rowland K, Mirchandani D, Bernath A, Camoriano J . Fulvestrant in women with advanced breast cancer after progression on prior aromatase inhibitor therapy: North Central Cancer Treatment Group Trial N0032. J Clin Oncol. 2006; 24(7):1052-6. DOI: 10.1200/JCO.2005.04.1053. View

De Greve J, Moran T, Graas M, Galdermans D, Vuylsteke P, Canon J . Phase II study of afatinib, an irreversible ErbB family blocker, in demographically and genotypically defined lung adenocarcinoma. Lung Cancer. 2015; 88(1):63-9. DOI: 10.1016/j.lungcan.2015.01.013. View

Madore J, Strbenac D, Vilain R, Menzies A, Yang J, Thompson J . PD-L1 Negative Status is Associated with Lower Mutation Burden, Differential Expression of Immune-Related Genes, and Worse Survival in Stage III Melanoma. Clin Cancer Res. 2016; 22(15):3915-23. DOI: 10.1158/1078-0432.CCR-15-1714. View

Zhu Q, Zhan P, Zhang X, Lv T, Song Y . Clinicopathologic characteristics of patients with ROS1 fusion gene in non-small cell lung cancer: a meta-analysis. Transl Lung Cancer Res. 2015; 4(3):300-9. PMC: 4483477. DOI: 10.3978/j.issn.2218-6751.2015.05.01. View

Morris S, Kirstein M, Valentine M, Dittmer K, Shapiro D, Saltman D . Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma. Science. 1994; 263(5151):1281-4. DOI: 10.1126/science.8122112. View

Grigg C, Rizvi N . PD-L1 biomarker testing for non-small cell lung cancer: truth or fiction?. J Immunother Cancer. 2016; 4:48. PMC: 4986262. DOI: 10.1186/s40425-016-0153-x. View

10.

Mano H . Non-solid oncogenes in solid tumors: EML4-ALK fusion genes in lung cancer. Cancer Sci. 2008; 99(12):2349-55. PMC: 11158085. DOI: 10.1111/j.1349-7006.2008.00972.x. View

11.

Campesato L, Barroso-Sousa R, Jimenez L, Correa B, Sabbaga J, Hoff P . Comprehensive cancer-gene panels can be used to estimate mutational load and predict clinical benefit to PD-1 blockade in clinical practice. Oncotarget. 2015; 6(33):34221-7. PMC: 4741447. DOI: 10.18632/oncotarget.5950. View

12.

Solomon B, Mok T, Kim D, Wu Y, Nakagawa K, Mekhail T . First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014; 371(23):2167-77. DOI: 10.1056/NEJMoa1408440. View

13.

Rizvi N, Hellmann M, Snyder A, Kvistborg P, Makarov V, Havel J . Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015; 348(6230):124-8. PMC: 4993154. DOI: 10.1126/science.aaa1348. View

14.

Herter-Sprie G, Greulich H, Wong K . Activating Mutations in ERBB2 and Their Impact on Diagnostics and Treatment. Front Oncol. 2013; 3:86. PMC: 3632856. DOI: 10.3389/fonc.2013.00086. View

15.

Takeuchi K, Soda M, Togashi Y, Suzuki R, Sakata S, Hatano S . RET, ROS1 and ALK fusions in lung cancer. Nat Med. 2012; 18(3):378-81. DOI: 10.1038/nm.2658. View

16.

Cho J, Kang M, Kim K . Epstein-Barr Virus-Associated Gastric Carcinoma and Specific Features of the Accompanying Immune Response. J Gastric Cancer. 2016; 16(1):1-7. PMC: 4834615. DOI: 10.5230/jgc.2016.16.1.1. View

17.

Mordechai O, Postovsky S, Vlodavsky E, Eran A, Constantini S, Dotan E . Metastatic rhabdoid meningioma with BRAF V600E mutation and good response to personalized therapy: case report and review of the literature. Pediatr Hematol Oncol. 2014; 32(3):207-11. DOI: 10.3109/08880018.2014.936058. View

18.

De Greve J, Teugels E, Geers C, Decoster L, Galdermans D, de Mey J . Clinical activity of afatinib (BIBW 2992) in patients with lung adenocarcinoma with mutations in the kinase domain of HER2/neu. Lung Cancer. 2012; 76(1):123-7. DOI: 10.1016/j.lungcan.2012.01.008. View

19.

Bouffet E, Larouche V, Campbell B, Merico D, De Borja R, Aronson M . Immune Checkpoint Inhibition for Hypermutant Glioblastoma Multiforme Resulting From Germline Biallelic Mismatch Repair Deficiency. J Clin Oncol. 2016; 34(19):2206-11. DOI: 10.1200/JCO.2016.66.6552. View

20.

Bowyer S, Rao A, Lyle M, Sandhu S, Long G, McArthur G . Activity of trametinib in K601E and L597Q BRAF mutation-positive metastatic melanoma. Melanoma Res. 2014; 24(5):504-8. DOI: 10.1097/CMR.0000000000000099. View