ArticleNature medicine2020
TMEM30A loss-of-function mutations drive lymphomagenesis and confer therapeutically exploitable vulnerability in B-cell lymphoma.
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Article in Nature medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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52citing papers in PubMed
4.2field-weighted citation impact, top 5% of its field
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52 citing papers in PubMed, 77 citations in OpenAlex.
- Cell surface remodeling caused by the loss of the flippase subunit TMEM30A in immune cells.Journal of cell science · 2026Article
- Clinical outcomes, patterns of relapse, and molecular landscape of advanced stage high-grade B-cell lymphoma.Blood advances · 2026Article
- Prognostic Role of SOCS1 Mutations in Diffuse Large B-Cell Lymphoma.Cancer research and treatment · 2026Article
- Phenotypic Characterization and Prognostic Impact of CD103+ Tissue-Resident Memory T Cells in Diffuse Large B-cell Lymphoma.Cancer immunology research · 2026Article
- Research progress on resistance mechanisms to CAR-T cell therapy in diffuse large B-cell lymphoma.Frontiers in oncology · 2026Review
- T follicular helper cells transiently unlock a plasticity state in germinal centre B cells during the humoral immune response.Nature cell biology · 2026Article
- Indole-3-Carbaldehyde fromResearch (Washington, D.C.) · 2026Article
- Molecular subtypes of DLBCL: are we ready to translate our knowledge into the change of treatment paradigms?Hematology. American Society of Hematology. Education Program · 2025Review
- Article
- Audit of B-cell cancer genes.Blood advances · 2025Review
- Molecular clustering on ctDNA improves the prognostic stratification of patients with DLBCL compared with ctDNA levels.Blood advances · 2025Observational
- Mitigating Early Phosphatidylserine Exposure in a Tmem30a-Dependent Way Ameliorates Neuronal Damages After Ischemic Stroke.MedComm · 2025Article
- Dys-regulated phosphatidylserine externalization as a cell intrinsic immune escape mechanism in cancer.Cell communication and signaling : CCS · 2025Review
- Recent advances in understanding of pathogenesis and treatment development for diffuse large B-cell lymphoma and follicular lymphoma.International journal of hematology · 2025Review
- Lymphoma cell-driven IL-16 is expressed in activated B-cell-like diffuse large B-cell lymphomas and regulates the pro-tumor microenvironment.Haematologica · 2025Article
- Substrates, regulation, cellular functions, and disease associations of P4-ATPases.Communications biology · 2025Review
- Overexpression of PLCG2 and TMEM38A inhibit tumor progression in clear cell renal cell carcinoma.Scientific reports · 2025Article
- EZB-type diffuse large B-cell lymphoma cell lines have superior migration capabilities compared to MCD-type.British journal of haematology · 2024Article
- Disruption of KLHL6 Fuels Oncogenic Antigen Receptor Signaling in B-Cell Lymphoma.Blood cancer discovery · 2024Article
- Functional and in silico analysis of ATP8A2 and other P4-ATPase variants associated with human genetic diseases.Disease models & mechanisms · 2024Article
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Authors and funding
57 authors at 9 institutions in 4 countries.
Daisuke Ennishi *Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada.
Shannon Healy *Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada.
Ali Bashashati *Molecular Oncology, British Columbia Cancer, Vancouver, British Columbia, Canada.
Saeed SaberiMolecular Oncology, British Columbia Cancer, Vancouver, British Columbia, Canada.
Christoffer HotherCentre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada.ORCID http://orcid.org/0000-0001-8778-9662
Anja MottokCentre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada.ORCID http://orcid.org/0000-0003-3125-0494
Fong Chun ChanCentre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada.
Lauren ChongCentre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada.
Libin AbrahamDepartment of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
Robert KridelCentre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada.ORCID http://orcid.org/0000-0003-0287-7124
Merrill BoyleCentre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada.
Barbara MeissnerCentre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada.
Tomohiro AokiCentre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada.ORCID http://orcid.org/0000-0001-6782-8361
Katsuyoshi TakataCentre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada.
Bruce W WoolcockCentre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada.
Elena ViganòCentre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada.
Michael GoldDepartment of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.ORCID http://orcid.org/0000-0003-1222-3191
Laurie L MoldayDepartment of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
Robert S MoldayDepartment of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.ORCID http://orcid.org/0000-0002-4479-1831
Adele TeleniusCentre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada.ORCID http://orcid.org/0000-0002-6901-5126
Michael Y LiCentre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada.
Nicole WrethamDepartment of Experimental Therapeutics, British Columbia Cancer, Vancouver, British Columbia, Canada.ORCID http://orcid.org/0000-0001-8942-4560
Nancy Dos SantosDepartment of Experimental Therapeutics, British Columbia Cancer, Vancouver, British Columbia, Canada.
Mark WongTrillium Therapeutics Inc., Mississauga, Ontario, Canada.
Natasja N VillerTrillium Therapeutics Inc., Mississauga, Ontario, Canada.
Robert A UgerTrillium Therapeutics Inc., Mississauga, Ontario, Canada.
Gerben DunsCentre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada.
Abigail BaticadosCentre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada.ORCID http://orcid.org/0000-0001-7990-8553
Angel MaderoCentre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada.
Brianna N BristowCentre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada.
Pedro FarinhaCentre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada.ORCID http://orcid.org/0000-0001-9364-9391
Graham W SlackCentre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada.
Susana Ben-NeriahCentre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada.
Daniel LaiMolecular Oncology, British Columbia Cancer, Vancouver, British Columbia, Canada.ORCID http://orcid.org/0000-0001-9203-6323
Allen W ZhangMolecular Oncology, British Columbia Cancer, Vancouver, British Columbia, Canada.ORCID http://orcid.org/0000-0002-7606-089X
Sohrab SalehiMolecular Oncology, British Columbia Cancer, Vancouver, British Columbia, Canada.
Hennady P ShulhaCentre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada.
Derek S ChiuDepartment of Statistics, University of British Columbia, Vancouver, British Columbia, Canada.
Sara MostafaviDepartment of Statistics, University of British Columbia, Vancouver, British Columbia, Canada.
Alina S GerrieCentre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada.
Da Wei HuangLymphoid Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Christopher RushtonDepartment of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada.
Diego VillaCentre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada.ORCID http://orcid.org/0000-0002-4625-3009
Laurie H SehnCentre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada.
Kerry J SavageCentre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada.
Andrew J MungallCanada's Michael Smith Genome Sciences Centre, British Columbia Cancer, Vancouver, British Columbia, Canada.ORCID http://orcid.org/0000-0002-0905-2742
Andrew P WengTerry Fox Laboratory, British Columbia Cancer, Vancouver, British Columbia, Canada.
Marcel B BallyDepartment of Experimental Therapeutics, British Columbia Cancer, Vancouver, British Columbia, Canada.
Ryan D MorinDepartment of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada.ORCID http://orcid.org/0000-0003-2932-7800
Gabriela V Cohen FreueDepartment of Statistics, University of British Columbia, Vancouver, British Columbia, Canada.
Louis M StaudtLymphoid Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Joseph M ConnorsCentre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada.
Marco A MarraDepartment of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.ORCID http://orcid.org/0000-0001-7146-7175
Sohrab P ShahMolecular Oncology, British Columbia Cancer, Vancouver, British Columbia, Canada.
Randy D GascoyneCentre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada.
David W ScottCentre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada. dscott8@bccancer.bc.ca.
Christian SteidlCentre for Lymphoid Cancer, British Columbia Cancer, Vancouver, British Columbia, Canada. CSteidl@bccancer.bc.ca.ORCID http://orcid.org/0000-0001-9842-9750
Spinal Cord Injury BC · CAUniversity of British Columbia · CABC Cancer Agency · CATrillium Therapeutics (Canada) · CANational Institutes of Health · USSimon Fraser University · CACanada's Michael Smith Genome Sciences Centre · CATerry Fox Research Institute · CAUniversität Ulm · DE
Funding
Oncogenic mechanisms and molecular targets in lymphomaZIABC011008 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI STAUDT, LOUIS · 2009 to 2025
$21.0MOncogenic mechanisms and molecular targets in lymphomaZ01BC011008 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI STAUDT, LOUIS · 2008 to 2008
$770kCIHR FDN-143288CIHR GP1-155873CIHR PJT-148649CIHR PJT-152946Intramural NIH HHS Z01 BC011008
Abstract
Transmembrane protein 30A (TMEM30A) maintains the asymmetric distribution of phosphatidylserine, an integral component of the cell membrane and 'eat-me' signal recognized by macrophages. Integrative genomic and transcriptomic analysis of diffuse large B-cell lymphoma (DLBCL) from the British Columbia population-based registry uncovered recurrent biallelic TMEM30A loss-of-function mutations, which were associated with a favorable outcome and uniquely observed in DLBCL. Using TMEM30A-knockout systems, increased accumulation of chemotherapy drugs was observed in TMEM30A-knockout cell lines and TMEM30A-mutated primary cells, explaining the improved treatment outcome. Furthermore, we found increased tumor-associated macrophages and an enhanced effect of anti-CD47 blockade limiting tumor growth in TMEM30A-knockout models. By contrast, we show that TMEM30A loss-of-function increases B-cell signaling following antigen stimulation-a mechanism conferring selective advantage during B-cell lymphoma development. Our data highlight a multifaceted role for TMEM30A in B-cell lymphomagenesis, and characterize intrinsic and extrinsic vulnerabilities of cancer cells that can be therapeutically exploited.
Indexed as
Loss of Function MutationMolecular Targeted TherapyAdolescentAdultAgedAged, 80 and overAnimalsBritish ColumbiaCells, CulturedCell Transformation, NeoplasticCohort StudiesFemaleGenetic Predisposition to DiseaseHEK293 CellsHumansJurkat CellsMembrane ProteinsTMEM30a protein, human
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