Ultra-Deep Sequencing Reveals the Mutational Landscape of Classical Hodgkin Lymphoma

Overview

Journal Cancer Res Commun

Specialty Oncology

Date 2023 Nov 1

PMID 37910143

Authors

Felicia Gomez

Bryan Fisk

Joshua F McMichael

Matthew Mosior

Jennifer A Foltz

Zachary L Skidmore

Eric J Duncavage

Christopher A Miller

Haley Abel

Yi-Shan Li

David A Russler-Germain

Kilannin Krysiak

Marcus P Watkins

Cody A Ramirez

Alina Schmidt

Fernanda Martins Rodrigues

Lee Trani

Ajay Khanna

Julia A Wagner

Robert S Fulton

Catrina C Fronick

Michelle D OLaughlin

Timothy Schappe

Amanda F Cashen

Neha Mehta-Shah

Brad S Kahl

Jason Walker

Nancy L Bartlett

Malachi Griffith

Todd A Fehniger

Obi L Griffith

Affiliations

Soon will be listed here.

Abstract

Significance: Our data demonstrate the utility of ultra-deep exome sequencing in uncovering somatic variants in Hodgkin lymphoma, creating new opportunities to define the genes that are recurrently mutated in this disease. We also show for the first time the successful application of snRNA-seq in Hodgkin lymphoma and describe the expression profile of a putative cluster of HRS cells in a single patient.

Citing Articles

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References

Thumkeo D, Watanabe S, Narumiya S . Physiological roles of Rho and Rho effectors in mammals. Eur J Cell Biol. 2013; 92(10-11):303-15. DOI: 10.1016/j.ejcb.2013.09.002. View

Liu Y, Abdul Razak F, Terpstra M, Chan F, Saber A, Nijland M . The mutational landscape of Hodgkin lymphoma cell lines determined by whole-exome sequencing. Leukemia. 2014; 28(11):2248-51. DOI: 10.1038/leu.2014.201. View

Dodt M, Roehr J, Ahmed R, Dieterich C . FLEXBAR-Flexible Barcode and Adapter Processing for Next-Generation Sequencing Platforms. Biology (Basel). 2014; 1(3):895-905. PMC: 4009805. DOI: 10.3390/biology1030895. View

Mottok A, Renne C, Seifert M, Oppermann E, Bechstein W, Hansmann M . Inactivating SOCS1 mutations are caused by aberrant somatic hypermutation and restricted to a subset of B-cell lymphoma entities. Blood. 2009; 114(20):4503-6. DOI: 10.1182/blood-2009-06-225839. View

Krimmel J, Schmitt M, Harrell M, Agnew K, Kennedy S, Emond M . Ultra-deep sequencing detects ovarian cancer cells in peritoneal fluid and reveals somatic TP53 mutations in noncancerous tissues. Proc Natl Acad Sci U S A. 2016; 113(21):6005-10. PMC: 4889384. DOI: 10.1073/pnas.1601311113. View

Nelms K, Keegan A, Zamorano J, Ryan J, Paul W . The IL-4 receptor: signaling mechanisms and biologic functions. Annu Rev Immunol. 1999; 17:701-38. DOI: 10.1146/annurev.immunol.17.1.701. View

Mata E, Diaz-Lopez A, Martin-Moreno A, Sanchez-Beato M, Varela I, Mestre M . Analysis of the mutational landscape of classic Hodgkin lymphoma identifies disease heterogeneity and potential therapeutic targets. Oncotarget. 2018; 8(67):111386-111395. PMC: 5762329. DOI: 10.18632/oncotarget.22799. View

Szydlowski M, Prochorec-Sobieszek M, Szumera-Cieckiewicz A, Derezinska E, Hoser G, Wasilewska D . Expression of PIM kinases in Reed-Sternberg cells fosters immune privilege and tumor cell survival in Hodgkin lymphoma. Blood. 2017; 130(12):1418-1429. DOI: 10.1182/blood-2017-01-760702. View

Aran D, Looney A, Liu L, Wu E, Fong V, Hsu A . Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage. Nat Immunol. 2019; 20(2):163-172. PMC: 6340744. DOI: 10.1038/s41590-018-0276-y. View

10.

Dejana E, Orsenigo F, Lampugnani M . The role of adherens junctions and VE-cadherin in the control of vascular permeability. J Cell Sci. 2008; 121(Pt 13):2115-22. DOI: 10.1242/jcs.017897. View

11.

Choi H, Zhang H, Park H, Choi K, Lee H, Agrawal V . Yes-associated protein regulates endothelial cell contact-mediated expression of angiopoietin-2. Nat Commun. 2015; 6:6943. DOI: 10.1038/ncomms7943. View

12.

Ryan N, Glaire M, Blake D, Cabrera-Dandy M, Evans D, Crosbie E . The proportion of endometrial cancers associated with Lynch syndrome: a systematic review of the literature and meta-analysis. Genet Med. 2019; 21(10):2167-2180. PMC: 8076013. DOI: 10.1038/s41436-019-0536-8. View

13.

Peng G, Dan W, Jun W, Junjun Y, Tong R, Baoli Z . Transcriptome profiling of the cancer and adjacent nontumor tissues from cervical squamous cell carcinoma patients by RNA sequencing. Tumour Biol. 2015; 36(5):3309-17. DOI: 10.1007/s13277-014-2963-0. View

14.

Kreis N, Louwen F, Yuan J . The Multifaceted p21 (Cip1/Waf1/) in Cell Differentiation, Migration and Cancer Therapy. Cancers (Basel). 2019; 11(9). PMC: 6770903. DOI: 10.3390/cancers11091220. View

15.

Younes A, Santoro A, Shipp M, Zinzani P, Timmerman J, Ansell S . Nivolumab for classical Hodgkin's lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial. Lancet Oncol. 2016; 17(9):1283-94. PMC: 5541855. DOI: 10.1016/S1470-2045(16)30167-X. View

16.

Yu F, Zhao B, Panupinthu N, Jewell J, Lian I, Wang L . Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling. Cell. 2012; 150(4):780-91. PMC: 3433174. DOI: 10.1016/j.cell.2012.06.037. View

17.

OHayre M, Inoue A, Kufareva I, Wang Z, Mikelis C, Drummond R . Inactivating mutations in GNA13 and RHOA in Burkitt's lymphoma and diffuse large B-cell lymphoma: a tumor suppressor function for the Gα13/RhoA axis in B cells. Oncogene. 2015; 35(29):3771-80. PMC: 4885800. DOI: 10.1038/onc.2015.442. View

18.

Zhou X, Chen N, Xu H, Zhou X, Wang J, Fang X . Regulation of Hippo-YAP signaling by insulin-like growth factor-1 receptor in the tumorigenesis of diffuse large B-cell lymphoma. J Hematol Oncol. 2020; 13(1):77. PMC: 7298789. DOI: 10.1186/s13045-020-00906-1. View

19.

Maziarz M, Federico A, Zhao J, Dujmusic L, Zhao Z, Monti S . Naturally occurring hotspot cancer mutations in Gα promote oncogenic signaling. J Biol Chem. 2020; 295(49):16897-16904. PMC: 7864081. DOI: 10.1074/jbc.AC120.014698. View

20.

Aoki T, Chong L, Takata K, Milne K, Hav M, Colombo A . Single-Cell Transcriptome Analysis Reveals Disease-Defining T-cell Subsets in the Tumor Microenvironment of Classic Hodgkin Lymphoma. Cancer Discov. 2019; 10(3):406-421. DOI: 10.1158/2159-8290.CD-19-0680. View