ArticleCancer discovery2023
Late-Stage Metastatic Melanoma Emerges through a Diversity of Evolutionary Pathways.
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Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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32citing papers in PubMed
10.2field-weighted citation impact, top 1% of its field
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Who cites it
32 citing papers in PubMed, 58 citations in OpenAlex.
- Explainable AI-Assisted Label-Free Raman Biosensing Reveals Therapy-Associated Spectral Signatures in Melanoma Tumors.Biosensors · 2026Article
- Intrapatient tumour heterogeneity and clonal evolution in an autopsy study of metastatic salivary gland cancer.Molecular oncology · 2026Article
- [Efficacy of CD4/TGF-β bispecific antibody in a mouse model of peritoneal metastasis of malignant melanoma].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Single-cell lineage tracing maps clonal and transcriptional dynamics in melanoma metastasis.bioRxiv : the preprint server for biology · 2026Article
- Evolution of Cancer Metastases via Lineage Trans-Differentiation.Research (Washington, D.C.) · 2026Article
- scCirclehunter delineates ecDNA-containing cells using single-cell ATAC-seq, with a focus on glioblastoma.Cell discovery · 2025Article
- Unravelling genomic differences in cerebrospinal fluid: patients with lung cancer with combined brain parenchymal and meningeal metastasis versus exclusive meningeal metastasis.Journal of neuro-oncology · 2025Article
- Loss of IDH1 and IDH2 mutations during the evolution of metastatic chondrosarcoma.Genome biology · 2025Article
- Cellular states associated with metastatic organotropism and survival in patients with pancreatic ductal adenocarcinoma.Nature genetics · 2025Article
- Long-read sequencing of single cell-derived melanoma subclones reveals divergent and parallel genomic and epigenomic evolutionary trajectories.bioRxiv : the preprint server for biology · 2025Article
- Interferon Epsilon Loss Is Elusive 9p21 Link to Immune-Cold Tumors, Resistant to Immune Checkpoint Therapy, and Endogenous CXCL9/10 Induction.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2025Review
- Multi-omic analysis of gallbladder cancer identifies distinct tumor microenvironments associated with disease progression.Nature genetics · 2025Article
- Patterns of intra- and intertumor phenotypic heterogeneity in lethal prostate cancer.The Journal of clinical investigation · 2025Article
- Metastatic Melanoma Prognosis Prediction Using a TC Radiomic-Based Machine Learning Model: A Preliminary Study.Cancers · 2025Article
- Article
- Tracking the Evolution of Cutaneous Melanoma by Multiparameter Flow Sorting and Genomic Profiling.International journal of molecular sciences · 2025Article
- The Dynamic Landscape of the Coagulome of Metastatic Malignant Melanoma.International journal of molecular sciences · 2025Article
- Punctuational evolution is pervasive in distal site metastatic colonization.Proceedings. Biological sciences · 2025Article
- Unveiling the mysteries of extrachromosomal circular DNA: from generation to clinical relevance in human cancers and health.Molecular cancer · 2024Review
- Genetic Characteristics of Cutaneous, Acral, and Mucosal Melanoma in Japan.Cancer medicine · 2024Article
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Authors and funding
71 authors at 9 institutions in 6 countries.
Lavinia Spain *Cancer Dynamics Laboratory, The Francis Crick Institute, London, United Kingdom.ORCID 0000-0002-9356-8812
Alexander Coulton *Cancer Dynamics Laboratory, The Francis Crick Institute, London, United Kingdom.ORCID 0000-0002-0826-5009
Irene Lobon *Cancer Dynamics Laboratory, The Francis Crick Institute, London, United Kingdom.ORCID 0000-0003-1170-9915
Andrew Rowan *Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, United Kingdom.ORCID 0000-0003-1926-9707
Desiree Schnidrig *Cancer Dynamics Laboratory, The Francis Crick Institute, London, United Kingdom.ORCID 0000-0002-7947-7666
Scott T C ShepherdCancer Dynamics Laboratory, The Francis Crick Institute, London, United Kingdom.ORCID 0000-0001-6208-173X
Benjamin ShumCancer Dynamics Laboratory, The Francis Crick Institute, London, United Kingdom.ORCID 0000-0003-4397-5580
Fiona ByrneCancer Dynamics Laboratory, The Francis Crick Institute, London, United Kingdom.ORCID 0000-0003-3800-0500
Maria GoicoecheaCancer Dynamics Laboratory, The Francis Crick Institute, London, United Kingdom.ORCID 0000-0003-3314-1179
Elisa PiperniCancer Dynamics Laboratory, The Francis Crick Institute, London, United Kingdom.ORCID 0000-0001-9361-7875
Lewis AuCancer Dynamics Laboratory, The Francis Crick Institute, London, United Kingdom.ORCID 0000-0001-5877-8657
Kim EdmondsThe Royal Marsden Hospital, London, United Kingdom.ORCID 0009-0006-1910-9518
Eleanor CarlyleThe Royal Marsden Hospital, London, United Kingdom.ORCID 0000-0003-3619-0742
Nikki HunterThe Royal Marsden Hospital, London, United Kingdom.ORCID 0009-0006-0825-3821
Alexandra RennThe Royal Marsden Hospital, London, United Kingdom.ORCID 0000-0001-5353-4346
Christina MessiouThe Royal Marsden Hospital, London, United Kingdom.ORCID 0000-0002-0557-9379
Peta HughesSkin and Renal Unit, Royal Marsden NHS Foundation Trust, London, United Kingdom.ORCID 0009-0009-7119-810X
Jaime NobbsSkin and Renal Unit, Royal Marsden NHS Foundation Trust, London, United Kingdom.ORCID 0009-0000-4539-569X
Floris FoijerEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands.ORCID 0000-0003-0989-3127
Hilda van den BosEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands.ORCID 0000-0001-9787-8597
Rene WardenaarEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands.ORCID 0000-0001-9891-1897
Diana C J SpieringsEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands.ORCID 0000-0001-8403-474X
Charlotte SpencerCancer Dynamics Laboratory, The Francis Crick Institute, London, United Kingdom.ORCID 0000-0003-1339-9922
Andreas M SchmittThe Royal Marsden Hospital, London, United Kingdom.ORCID 0000-0002-9568-8164
Zayd TippuCancer Dynamics Laboratory, The Francis Crick Institute, London, United Kingdom.ORCID 0000-0002-3602-0770
Karla LingardThe Royal Marsden Hospital, London, United Kingdom.ORCID 0009-0004-3660-7936
Lauren GrostateThe Royal Marsden Hospital, London, United Kingdom.ORCID 0009-0006-1807-0025
Kema PeatThe Royal Marsden Hospital, London, United Kingdom.ORCID 0009-0000-6063-6498
Kayleigh KellyThe Royal Marsden Hospital, London, United Kingdom.ORCID 0009-0005-1285-2029
Sarah SarkerThe Royal Marsden Hospital, London, United Kingdom.ORCID 0000-0001-5313-1045
Sarah VaughanThe Royal Marsden Hospital, London, United Kingdom.ORCID 0009-0002-0294-5107
Mary MangwendeThe Royal Marsden Hospital, London, United Kingdom.ORCID 0009-0001-7670-2231
Lauren TerryThe Royal Marsden Hospital, London, United Kingdom.ORCID 0009-0001-5060-7279
Denise KellyThe Royal Marsden Hospital, London, United Kingdom.ORCID 0009-0003-3401-6633
Jennifer BianoThe Royal Marsden Hospital, London, United Kingdom.ORCID 0009-0000-5492-9681
Aida MurraThe Royal Marsden Hospital, London, United Kingdom.ORCID 0009-0007-9524-7995
Justine KortewegThe Royal Marsden Hospital, London, United Kingdom.ORCID 0009-0002-4665-0968
Charlotte LewisThe Royal Marsden Hospital, London, United Kingdom.ORCID 0009-0000-8033-9458
Molly O'FlahertyThe Royal Marsden Hospital, London, United Kingdom.ORCID 0009-0006-4015-839X
Anne-Laure CattinCancer Dynamics Laboratory, The Francis Crick Institute, London, United Kingdom.ORCID 0000-0001-7512-9173
Max EmmerichCancer Dynamics Laboratory, The Francis Crick Institute, London, United Kingdom.ORCID 0000-0002-2026-974X
Camille L GerardCancer Dynamics Laboratory, The Francis Crick Institute, London, United Kingdom.ORCID 0000-0002-6007-1746
Husayn Ahmed PallikondaCancer Dynamics Laboratory, The Francis Crick Institute, London, United Kingdom.ORCID 0000-0003-4472-2067
Joanna LynchThe Royal Marsden Hospital, London, United Kingdom.ORCID 0009-0005-7776-4396
Robert MasonGold Coast University Hospital, Queensland, Australia.ORCID 0000-0001-8055-9936
Aljosja RogiersCancer Dynamics Laboratory, The Francis Crick Institute, London, United Kingdom.ORCID 0000-0002-3807-9696
Hang XuThe Francis Crick Institute, London, United Kingdom.ORCID 0000-0002-5847-655X
Ariana HuebnerCancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, United Kingdom.ORCID 0000-0001-8009-4999
Nicholas McGranahanCancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, UCL Cancer Institute, London, United Kingdom.ORCID 0000-0001-9537-4045
Maise Al BakirCancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, United Kingdom.ORCID 0000-0002-0846-8332
Jun MuraiTumour Immunogenomics and Immunosurveillance (TIGI) Lab, UCL Cancer Institute, London, United Kingdom.ORCID 0000-0002-1322-0796
Cristina Naceur-LombardelliCancer Research UK Lung Cancer Centre of Excellence, UCL Cancer Institute, London, United Kingdom.ORCID 0000-0002-7097-0307
Elaine BorgUniversity College London Hospital, London, United Kingdom.ORCID 0009-0000-6250-9695
Miriam MitchisonUniversity College London Hospital, London, United Kingdom.ORCID 0000-0003-2520-2744
David A MooreGuy's and St Thomas' NHS Foundation Trust, London, United Kingdom.ORCID 0000-0002-6296-1312
Mary FalzonUniversity College London Hospital, London, United Kingdom.ORCID 0009-0006-6210-4376
Ian ProctorUniversity College London Hospital, London, United Kingdom.ORCID 0009-0006-3091-9124
Gordon W H StampThe Francis Crick Institute, London, United Kingdom.ORCID 0000-0003-2888-4314
Emma L NyeThe Francis Crick Institute, London, United Kingdom.ORCID 0000-0001-9154-3526
Kate YoungSkin and Renal Unit, Royal Marsden NHS Foundation Trust, London, United Kingdom.ORCID 0000-0002-9500-2046
Andrew J S FurnessSkin and Renal Unit, Royal Marsden NHS Foundation Trust, London, United Kingdom.ORCID 0000-0002-2358-9730
Lisa PickeringThe Royal Marsden Hospital, London, United Kingdom.ORCID 0000-0002-7579-340X
Ruby StewartGuy's and St Thomas' NHS Foundation Trust, London, United Kingdom.ORCID 0009-0003-2253-1611
Ula MahadevaGuy's and St Thomas' NHS Foundation Trust, London, United Kingdom.ORCID 0000-0002-9459-3403
Anna GreenGuy's and St Thomas' NHS Foundation Trust, London, United Kingdom.ORCID 0000-0002-1241-4230
James LarkinGuy's and St Thomas' NHS Foundation Trust, London, United Kingdom.ORCID 0000-0001-5569-9523
Kevin Litchfield *Tumour Immunogenomics and Immunosurveillance (TIGI) Lab, UCL Cancer Institute, London, United Kingdom.ORCID 0000-0002-3725-0914
Charles Swanton *Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, United Kingdom.ORCID 0000-0002-4299-3018
Mariam Jamal-Hanjani *Cancer Research UK Lung Cancer Centre of Excellence, UCL Cancer Institute, London, United Kingdom.ORCID 0000-0003-1212-1259
PEACE Consortium
Samra Turajlic *Cancer Dynamics Laboratory, The Francis Crick Institute, London, United Kingdom.ORCID 0000-0001-8846-136X
Royal Marsden NHS Foundation Trust · GBThe Francis Crick Institute · GBRoyal Marsden Hospital · GBGuy's and St Thomas' NHS Foundation Trust · GBUniversity College Hospital · GBInstitute of Cancer Research · GBUniversity Medical Center Groningen · NLCRUK Lung Cancer Centre of Excellence · GBGold Coast Hospital · AU
Funding
Deciphering Clonal Evolution in Hereditary Renal Cell CarcinomasU01CA247439 · NCI · FRANCIS CRICK INSTITUTE, LTD · PI TURAJLIC, SAMRA · 2020 to 2024
$1.1MCancer Research UK 17786Cancer Research UK 21999Cancer Research UK 29911Cancer Research UK 30025Cancer Research UK A29911Cancer Research UK C11496/A17786Cancer Research UK C11496/A30025Cancer Research UK C69256/A30194Cancer Research UK FC10988Medical Research Council FC10988Medical Research Council MR/P014712/1Medical Research Council MR/V033077/1NCI NIH HHS U01 CA247439Wellcome Trust FC001169Wellcome Trust FC10988
Abstract
Understanding the evolutionary pathways to metastasis and resistance to immune-checkpoint inhibitors (ICI) in melanoma is critical for improving outcomes. Here, we present the most comprehensive intrapatient metastatic melanoma dataset assembled to date as part of the Posthumous Evaluation of Advanced Cancer Environment (PEACE) research autopsy program, including 222 exome sequencing, 493 panel-sequenced, 161 RNA sequencing, and 22 single-cell whole-genome sequencing samples from 14 ICI-treated patients. We observed frequent whole-genome doubling and widespread loss of heterozygosity, often involving antigen-presentation machinery. We found KIT extrachromosomal DNA may have contributed to the lack of response to KIT inhibitors of a KIT-driven melanoma. At the lesion-level, MYC amplifications were enriched in ICI nonresponders. Single-cell sequencing revealed polyclonal seeding of metastases originating from clones with different ploidy in one patient. Finally, we observed that brain metastases that diverged early in molecular evolution emerge late in disease. Overall, our study illustrates the diverse evolutionary landscape of advanced melanoma. SIGNIFICANCE: Despite treatment advances, melanoma remains a deadly disease at stage IV. Through research autopsy and dense sampling of metastases combined with extensive multiomic profiling, our study elucidates the many mechanisms that melanomas use to evade treatment and the immune system, whether through mutations, widespread copy-number alterations, or extrachromosomal DNA. See related commentary by Shain, p. 1294. This article is highlighted in the In This Issue feature, p. 1275.
Indexed as
Brain NeoplasmsMelanomaDNAEvolution, MolecularHumansMutationDNA
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