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Review
. 2022 Dec:6:e2200245.
doi: 10.1200/PO.22.00245.

Implementation of Whole-Genome and Transcriptome Sequencing Into Clinical Cancer Care

Edwin Cuppen  1   2 , Olivier Elemento  3 , Richard Rosenquist  4   5 , Svetlana Nikic  6 , Maarten IJzerman  7   8 , Isabelle Durand Zaleski  9 , Geert Frederix  10 , Lars-Åke Levin  11 , Charles G Mullighan  12 , Reinhard Buettner  13 , Trevor J Pugh  14   15   16 , Sean Grimmond  8 , Carlos Caldas  17 , Fabrice Andre  18 , Ilse Custers  19 , Elias Campo  20   21   22   23 , Hans van Snellenberg  1 , Anna Schuh  24 , Hidewaki Nakagawa  25 , Christof von Kalle  26 , Torsten Haferlach  27 , Stefan Fröhling  28   29 , Vaidehi Jobanputra  30
Affiliations
Review

Implementation of Whole-Genome and Transcriptome Sequencing Into Clinical Cancer Care

Edwin Cuppen et al. JCO Precis Oncol. 2022 Dec.

Abstract

Purpose: The combination of whole-genome and transcriptome sequencing (WGTS) is expected to transform diagnosis and treatment for patients with cancer. WGTS is a comprehensive precision diagnostic test that is starting to replace the standard of care for oncology molecular testing in health care systems around the world; however, the implementation and widescale adoption of this best-in-class testing is lacking.

Methods: Here, we address the barriers in integrating WGTS for cancer diagnostics and treatment selection and answer questions regarding utility in different cancer types, cost-effectiveness and affordability, and other practical considerations for WGTS implementation.

Results: We review the current studies implementing WGTS in health care systems and provide a synopsis of the clinical evidence and insights into practical considerations for WGTS implementation. We reflect on regulatory, costs, reimbursement, and incidental findings aspects of this test.

Conclusion: WGTS is an appropriate comprehensive clinical test for many tumor types and can replace multiple, cascade testing approaches currently performed. Decreasing sequencing cost, increasing number of clinically relevant aberrations and discovery of more complex biomarkers of treatment response, should pave the way for health care systems and laboratories in implementing WGTS into clinical practice, to transform diagnosis and treatment for patients with cancer.

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Conflict of interest statement

Edwin CuppenConsulting or Advisory Role: Illumina (Inst), InteRNATravel, Accommodations, Expenses: Illumina Olivier ElementoStock and Other Ownership Interests: Volastra Therapeutics, Owkin, OneThree Biotech Richard RosenquistHonoraria: AbbVie, Illumina, Roche, Janssen, AstraZenecaConsulting or Advisory Role: Illumina, AbbVieTravel, Accommodations, Expenses: Illumina Svetlana NikicEmployment: IlluminaStock and Other Ownership Interests: Illumina Maarten IJzermanHonoraria: RTI Health Solutions, IlluminaConsulting or Advisory Role: Creativ-Ceutical, Illumina (Inst)Research Funding: Illumina (Inst)Travel, Accommodations, Expenses: Illumina (Inst) Isabelle Durand ZaleskiHonoraria: Abbott Laboratories, BMS, MSD Oncology, Pfizer, IlluminaConsulting or Advisory Role: BMS, MSD Oncology, Pfizer Geert FrederixHonoraria: Illumina (Inst)Consulting or Advisory Role: Illumina (Inst) Lars-Åke LevinEmployment: JanssenStock and Other Ownership Interests: AstraZenecaResearch Funding: Boehringer Ingelheim (Inst), Janssen (Inst) Charles G. MullighanStock and Other Ownership Interests: AmgenHonoraria: Amgen, IlluminaConsulting or Advisory Role: Illumina, Faze, Beam TherapeuticsSpeakers' Bureau: Amgen, PfizerResearch Funding: Loxo, Pfizer, AbbViePatents, Royalties, Other Intellectual Property: Inventor on a pending patent application related to gene-expression signatures for detection of underlying Philadelphia chromosome “like events and therapeutic targeting in leukemia (PCT/US2012/069228), WO 2021/022076 A1. This Patent Highlight shows representative PROTAC compounds bound to JAK2, where ruxolitinib and baricitinib bind to the human JAK2 JH1. Furthermore, representative data illustrate protein degradation, cytotoxicity, and effect of the JAKSTAT signaling pathway of the PROTAC compounds in MHHCALL-4 cells, Marcus Fisher, Fatemeh Keramatnia, Kevin Mcgowan, Jaeki Min, Gisele A. Nishiguchi, Jeanine Price, Zoran Rankovic, Das Sourav, Charles G. Mullighan, Yunchao Chang 2021 Substituted N-(2-(2,6-Dioxopiperidin-3-YL)-1,3-Dioxoisoindolin-5-YL)Arylsulfonamide Analogs as Modulators of Cereblon Protein, Application No: PCT/US2021/051648 Filed: September 23, 2021. Patent pending (Inst)Travel, Accommodations, Expenses: Amgen, Illumina Reinhard BuettnerStock and Other Ownership Interests: Gnothis IncHonoraria: AstraZeneca, AbbVie, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Merck Serono, MSD, Novartis, Qiagen, Pfizer, Roche, IlluminaResearch Funding: Roche (Inst) Trevor J. PughHonoraria: Merck, AstraZeneca, Illumina, PACT PharmaConsulting or Advisory Role: Chrysalis Biomedical Advisors, Axiom Healthcare Strategies, Canadian Pension Plan Investment BoardResearch Funding: RochePatents, Royalties, Other Intellectual Property: Hybrid-capture sequencing for dete rmining immune cell clonality Carlos CaldasConsulting or Advisory Role: AstraZeneca/MedImmune, IlluminaResearch Funding: AstraZeneca (Inst), Genentech/Roche (Inst), Servier (Inst) Fabrice AndreStock and Other Ownership Interests: PEGASCYConsulting or Advisory Role: Guardant Health (Inst), MedImmune (Inst), Gilead Sciences (Inst), Relay therapeutics (Inst)Research Funding: AstraZeneca (Inst), Novartis (Inst), Pfizer (Inst), Lilly (Inst), Roche (Inst), Daiichi (Inst)Travel, Accommodations, Expenses: Novartis, Roche, GlaxoSmithKline, AstraZeneca Ilse CustersHonoraria: IlluminaTravel, Accommodations, Expenses: Illumina Elias CampoHonoraria: EUSA Pharma, AstraZeneca, TakedaConsulting or Advisory Role: Illumina, AbbVieResearch Funding: AstraZenecaPatents, Royalties, Other Intellectual Property: Author on a patent licensed to NanoStrig Technologies, Author in the protectedt bioinformatic IgCaller pipeline Hans van SnellenbergResearch Funding: Illumina (Inst) Anna SchuhStock and Other Ownership Interests: Illumina, SERENOxConsulting or Advisory Role: AbbVie, Roche, Janssen, AstraZenecaResearch Funding: Johnson & Johnson, Illumina (Inst), Oxford Nanopore Technologies (Inst)Travel, Accommodations, Expenses: AbbVie, Janssen Oncology Christof von KalleStock and Other Ownership Interests: GeneWerkConsulting or Advisory Role: Roche/Genentech, Novartis, PfizerPatents, Royalties, Other Intellectual Property: Patent applications in molecular diagnostics Torsten HaferlachEmployment: MLL Munich Leukemia LaboratoryLeadership: MLL Munich Leukemia LaboratoryConsulting or Advisory Role: Illumina Stefan FröhlingHonoraria: PharmaMar, Roche, Lilly, AmgenConsulting or Advisory Role: Bayer, Illumina, RocheResearch Funding: AstraZeneca (Inst), PharmaMar (Inst), Pfizer (Inst), Roche (Inst)Travel, Accommodations, Expenses: PharmaMar, Roche, Lilly, Amgen Vaidehi JobanputraHonoraria: IlluminaNo other potential conflicts of interest were reported.

Figures

FIG 1.
FIG 1.
Methods currently used for a precise diagnosis of patients with cancer and tumor characterization. aMethod/design-specific limitations may exist in sensitivity and/or event type or size. bOnly when a normal control is included in the test, which is not routine practice. cAlthough the approach is genome-wide, the analysis is usually done in targeted way because of the complexity of analysis. CMA, chromosomal microarray; CNAs, copy number aberrations; Diff. Expr., differential expressions; FISH, fluorescence in situ hybridization; GEX, gene expression; HLA, human leukocyte antigen; HRD, homologous recombination deficiency; HRR, homologous recombination repair; MSI, microsatellite instability; PGX, pharmacogenomics; SNVs, single-nucleotide variants; TMB, tumor mutational burden; TME, tumor mutational environment; WES, whole-exome sequencing; WGS, whole-genome sequencing; WGTS, whole-genome and transcriptome sequencing; WTS, whole-transcriptome sequencing.
FIG 2.
FIG 2.
Centralized approach enabling effective WGTS-based precision medicine. FF, fresh frozen; FFPE, formalin-fixed paraffin-embedded; WGS, whole-genome sequencing; WGTS, whole-genome transcriptome sequencing.
See this image and copyright information in PMC

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