Validation of Clinical-grade Whole Genome Sequencing Reproduces Cytogenetic Analysis and Identifies Mutational Landscape in Newly-diagnosed Multiple Myeloma Patients: A Pilot Study from the 100,000 Genomes Project

Overview

Journal EJHaem

Specialty Hematology

Date 2022 Jul 18

PMID 35845211

Authors

Oliver C Lomas

Sarah Gooding

Maite Cabes

Helene Dreau

Edward Wilson

Paolo Polzella

Karthik Ramasamy

Angela D Hamblin

Affiliations

Soon will be listed here.

Abstract

Multiple myeloma is characterized by chromosomal abnormalities and genetic variation, which may inform prognosis and guide treatment. This pilot study sought to examine the feasibility of incorporating Whole Genome Sequencing (WGS) alongside the routine laboratory evaluation of 14 patients with newly diagnosed multiple myeloma who had enrolled in the 100,000 Genomes Project. In all 14 cases, WGS data could be obtained in a timely fashion within existing clinical frameworks in a tertiary hospital setting. The data not only replicated standard-of-care FISH analysis of chromosomal abnormalities but also provided further chromosomal and molecular genetic insights that may influence patient management.

Citing Articles

The potential clinical utility of Whole Genome Sequencing for patients with cancer: evaluation of a regional implementation of the 100,000 Genomes Project.

Leung E, Robbins H, Zaman S, Lal N, Morton D, Dew L Br J Cancer. 2024; 131(11):1805-1813.

PMID: 39478124 PMC: 11589591. DOI: 10.1038/s41416-024-02890-6.

Quantitative Integrative Survival Prediction in Multiple Myeloma Patients Treated With Bortezomib-Based Induction, High-Dose Therapy and Autologous Stem Cell Transplantation.

Hummel M, Hielscher T, Emde-Rajaratnam M, Salwender H, Beck S, Scheid C JCO Precis Oncol. 2024; 8:e2300613.

PMID: 38986047 PMC: 11371111. DOI: 10.1200/PO.23.00613.

RNA-sequencing based first choice of treatment and determination of risk in multiple myeloma.

Emde-Rajaratnam M, Beck S, Benes V, Salwender H, Bertsch U, Scheid C Front Immunol. 2023; 14:1286700.

PMID: 38035078 PMC: 10684778. DOI: 10.3389/fimmu.2023.1286700.

Application of R2-ISS risk stratification to patients with multiple myeloma treated with autologous stem cell transplants at UAMS.

Guo W, Zhan A, Mery D, Munshi M, Makhoul O, Baily C Blood Adv. 2023; 7(21):6676-6684.

PMID: 37756524 PMC: 10637884. DOI: 10.1182/bloodadvances.2023011096.

Multiple Myeloma With Amplification of Chr1q: Therapeutic Opportunity and Challenges.

Sklavenitis-Pistofidis R, Getz G, Ghobrial I, Papaioannou M Front Oncol. 2022; 12:961421.

PMID: 35912171 PMC: 9331166. DOI: 10.3389/fonc.2022.961421.

References

Gooding S, Ansari-Pour N, Towfic F, Estevez M, Chamberlain P, Tsai K . Multiple cereblon genetic changes are associated with acquired resistance to lenalidomide or pomalidomide in multiple myeloma. Blood. 2021; 137(2):232-237. PMC: 7893409. DOI: 10.1182/blood.2020007081. View

Chng W, Dispenzieri A, Chim C, Fonseca R, Goldschmidt H, Lentzsch S . IMWG consensus on risk stratification in multiple myeloma. Leukemia. 2013; 28(2):269-77. DOI: 10.1038/leu.2013.247. View

Russell L, De Castro D, Griffiths M, Telford N, Bernard O, Panzer-Grumayer R . A novel translocation, t(14;19)(q32;p13), involving IGH@ and the cytokine receptor for erythropoietin. Leukemia. 2008; 23(3):614-7. DOI: 10.1038/leu.2008.250. View

Gonzalez-Calle V, Keane N, Braggio E, Fonseca R . Precision Medicine in Myeloma: Challenges in Defining an Actionable Approach. Clin Lymphoma Myeloma Leuk. 2017; 17(10):621-630. DOI: 10.1016/j.clml.2017.06.021. View

Wuilleme S, Robillard N, Lode L, Magrangeas F, Beris H, Harousseau J . Ploidy, as detected by fluorescence in situ hybridization, defines different subgroups in multiple myeloma. Leukemia. 2004; 19(2):275-8. DOI: 10.1038/sj.leu.2403586. View

Sharma N, Smadbeck J, Abdallah N, Zepeda-Mendoza C, Binder M, Pearce K . The Prognostic Role of MYC Structural Variants Identified by NGS and FISH in Multiple Myeloma. Clin Cancer Res. 2021; 27(19):5430-5439. PMC: 8738776. DOI: 10.1158/1078-0432.CCR-21-0005. View

Chapman M, Lawrence M, Keats J, Cibulskis K, Sougnez C, Schinzel A . Initial genome sequencing and analysis of multiple myeloma. Nature. 2011; 471(7339):467-72. PMC: 3560292. DOI: 10.1038/nature09837. View

Kumar S, Harrison S, Cavo M, Rubia J, Popat R, Gasparetto C . Venetoclax or placebo in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (BELLINI): a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2020; 21(12):1630-1642. DOI: 10.1016/S1470-2045(20)30525-8. View

Anderson K, Auclair D, Kelloff G, Sigman C, Avet-Loiseau H, Farrell A . The Role of Minimal Residual Disease Testing in Myeloma Treatment Selection and Drug Development: Current Value and Future Applications. Clin Cancer Res. 2017; 23(15):3980-3993. DOI: 10.1158/1078-0432.CCR-16-2895. View

10.

Walker B, Wardell C, Brioli A, Boyle E, Kaiser M, Begum D . Translocations at 8q24 juxtapose MYC with genes that harbor superenhancers resulting in overexpression and poor prognosis in myeloma patients. Blood Cancer J. 2014; 4:e191. PMC: 3972699. DOI: 10.1038/bcj.2014.13. View

11.

Hayami Y, Iida S, Nakazawa N, Hanamura I, Kato M, Komatsu H . Inactivation of the E3/LAPTm5 gene by chromosomal rearrangement and DNA methylation in human multiple myeloma. Leukemia. 2003; 17(8):1650-7. DOI: 10.1038/sj.leu.2403026. View

12.

Carrasco D, Tonon G, Huang Y, Zhang Y, Sinha R, Feng B . High-resolution genomic profiles define distinct clinico-pathogenetic subgroups of multiple myeloma patients. Cancer Cell. 2006; 9(4):313-25. DOI: 10.1016/j.ccr.2006.03.019. View

13.

Lomas O, Gooding S, Cabes M, Dreau H, Wilson E, Polzella P . Validation of clinical-grade whole genome sequencing reproduces cytogenetic analysis and identifies mutational landscape in newly-diagnosed multiple myeloma patients: A pilot study from the 100,000 Genomes Project. EJHaem. 2022; 2(4):809-812. PMC: 9175844. DOI: 10.1002/jha2.276. View

14.

Boyd K, Ross F, Walker B, Wardell C, Tapper W, Chiecchio L . Mapping of chromosome 1p deletions in myeloma identifies FAM46C at 1p12 and CDKN2C at 1p32.3 as being genes in regions associated with adverse survival. Clin Cancer Res. 2011; 17(24):7776-84. PMC: 5751883. DOI: 10.1158/1078-0432.CCR-11-1791. View

15.

Lohr J, Stojanov P, Carter S, Cruz-Gordillo P, Lawrence M, Auclair D . Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy. Cancer Cell. 2014; 25(1):91-101. PMC: 4241387. DOI: 10.1016/j.ccr.2013.12.015. View