Validation of a Targeted Next-Generation Sequencing Panel for Tumor Mutation Burden Analysis: Results from the Onconetwork Immuno-Oncology Consortium.

The Journal of Molecular Diagnostics : JMD
Francesca FeniziaNicola Normanno

Abstract

Tumor mutation burden (TMB) is evaluated as a biomarker of response to immunotherapy. We present the efforts of the Onconetwork Immuno-Oncology Consortium to validate a commercial targeted sequencing test for TMB calculation. A three-phase study was designed to validate the Oncomine Tumor Mutational Load (OTML) assay at nine European laboratories. Phase 1 evaluated reproducibility and accuracy on seven control samples. In phase 2, six formalin-fixed, paraffin-embedded samples tested with FoundationOne were reanalyzed with the OTML panel to evaluate concordance and reproducibility. Phase 3 involved analysis of 90 colorectal cancer samples with known microsatellite instability (MSI) status to evaluate TMB and MSI association. High reproducibility of TMB was demonstrated among the sites in the first and second phases. Strong correlation was also detected between mean and expected TMB in phase 1 (r2 = 0.998) and phase 2 (r2 = 0.96). Detection of actionable mutations was also confirmed. In colorectal cancer samples, the expected pattern of MSI-high/high-TMB and microsatellite stability/low-TMB was present, and gene signatures produced by the panel suggested the presence of a POLE mutation in two samples. The OTML panel demonstrated ...Continue Reading

References

Apr 20, 2017·Genome Medicine·Zachary R ChalmersGarrett M Frampton
Dec 21, 2017·The New England Journal of Medicine·Mark YarchoanElizabeth M Jaffee
Apr 15, 2018·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Yuki Owada-OzakiHiroyuki Suzuki
Oct 13, 2018·Science·Razvan CristescuDavid Kaufman
Feb 23, 2019·ESMO Open·Reinhard BüttnerFrédérique Penault-Llorca
Mar 14, 2019·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Federico InnocentiOmar Kabbarah
Jul 17, 2019·Journal for Immunotherapy of Cancer·Laura FancelloLuca Mazzarella
Nov 5, 2019·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Aurelien MarabelleLuis A Diaz
Jan 29, 2020·Annals of Oncology : Official Journal of the European Society for Medical Oncology·A B SchrockM Fakih
Feb 7, 2020·Nature·Ludmil B AlexandrovUNKNOWN PCAWG Consortium
Mar 3, 2020·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Albrecht StenzingerManfred Dietel
Jun 27, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Arsen OsipovMark Yarchoan

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.