dc.contributor.author | Spain, L | |
dc.contributor.author | Coulton, A | |
dc.contributor.author | Lobon, I | |
dc.contributor.author | Rowan, A | |
dc.contributor.author | Schnidrig, D | |
dc.contributor.author | Shepherd, STC | |
dc.contributor.author | Shum, B | |
dc.contributor.author | Byrne, F | |
dc.contributor.author | Goicoechea, M | |
dc.contributor.author | Piperni, E | |
dc.contributor.author | Au, L | |
dc.contributor.author | Edmonds, K | |
dc.contributor.author | Carlyle, E | |
dc.contributor.author | Hunter, N | |
dc.contributor.author | Renn, A | |
dc.contributor.author | Messiou, C | |
dc.contributor.author | Hughes, P | |
dc.contributor.author | Nobbs, J | |
dc.contributor.author | Foijer, F | |
dc.contributor.author | van den Bos, H | |
dc.contributor.author | Wardenaar, R | |
dc.contributor.author | Spierings, DCJ | |
dc.contributor.author | Spencer, C | |
dc.contributor.author | Schmitt, AM | |
dc.contributor.author | Tippu, Z | |
dc.contributor.author | Lingard, K | |
dc.contributor.author | Grostate, L | |
dc.contributor.author | Peat, K | |
dc.contributor.author | Kelly, K | |
dc.contributor.author | Sarker, S | |
dc.contributor.author | Vaughan, S | |
dc.contributor.author | Mangwende, M | |
dc.contributor.author | Terry, L | |
dc.contributor.author | Kelly, D | |
dc.contributor.author | Biano, J | |
dc.contributor.author | Murra, A | |
dc.contributor.author | Korteweg, J | |
dc.contributor.author | Lewis, C | |
dc.contributor.author | O'Flaherty, M | |
dc.contributor.author | Cattin, A-L | |
dc.contributor.author | Emmerich, M | |
dc.contributor.author | Gerard, CL | |
dc.contributor.author | Pallikonda, HA | |
dc.contributor.author | Lynch, J | |
dc.contributor.author | Mason, R | |
dc.contributor.author | Rogiers, A | |
dc.contributor.author | Xu, H | |
dc.contributor.author | Huebner, A | |
dc.contributor.author | McGranahan, N | |
dc.contributor.author | Al Bakir, M | |
dc.contributor.author | Murai, J | |
dc.contributor.author | Naceur-Lombardelli, C | |
dc.contributor.author | Borg, E | |
dc.contributor.author | Mitchison, M | |
dc.contributor.author | Moore, DA | |
dc.contributor.author | Falzon, M | |
dc.contributor.author | Proctor, I | |
dc.contributor.author | Stamp, GWH | |
dc.contributor.author | Nye, EL | |
dc.contributor.author | Young, K | |
dc.contributor.author | Furness, AJS | |
dc.contributor.author | Pickering, L | |
dc.contributor.author | Stewart, R | |
dc.contributor.author | Mahadeva, U | |
dc.contributor.author | Green, A | |
dc.contributor.author | Larkin, J | |
dc.contributor.author | Litchfield, K | |
dc.contributor.author | Swanton, C | |
dc.contributor.author | Jamal-Hanjani, M | |
dc.contributor.author | PEACE Consortium, | |
dc.contributor.author | Turajlic, S | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2023-05-18T14:56:01Z | |
dc.date.available | 2023-05-18T14:56:01Z | |
dc.date.issued | 2023-06-02 | |
dc.identifier | 719029 | |
dc.identifier.citation | Cancer Discovery, 2023, pp. CD-22-1427 - | |
dc.identifier.issn | 2159-8274 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5787 | |
dc.identifier.eissn | 2159-8290 | |
dc.identifier.eissn | 2159-8290 | |
dc.identifier.doi | 10.1158/2159-8290.CD-22-1427 | |
dc.description.abstract | UNLABELLED: 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. | |
dc.format | Print-Electronic | |
dc.format.extent | CD-22-1427 - | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER ASSOC CANCER RESEARCH | |
dc.relation.ispartof | Cancer Discovery | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.title | Late-Stage Metastatic Melanoma Emerges through a Diversity of Evolutionary Pathways. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2023-03-17 | |
dc.date.updated | 2023-05-18T14:54:28Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1158/2159-8290.CD-22-1427 | |
rioxxterms.licenseref.startdate | 2023-03-28 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/36977461 | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Cell Death and Immunity | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Melanoma and Kidney Cancer | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Closed research teams | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Closed research teams/Experimental Pathology | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Melanoma and Kidney Cancer/Melanoma and Kidney Cancer (hon.) | |
pubs.organisational-group | /ICR/Students | |
pubs.organisational-group | /ICR/Students/PhD and MPhil | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/18/19 Starting Cohort | |
pubs.organisational-group | /ICR/ImmNet | |
pubs.organisational-group | /ICR/Students/MD(Res) | |
pubs.organisational-group | /ICR/Students/MD(Res)/Starting Cohort 20/21 | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/22/23 Starting Cohort | |
pubs.publication-status | Published online | |
pubs.publisher-url | http://dx.doi.org/10.1158/2159-8290.cd-22-1427 | |
icr.researchteam | Melanoma & Kidney Cancer | |
icr.researchteam | Cell Death and Immunity | |
icr.researchteam | Experimental Pathology | |
icr.researchteam | Skin Unit | |
dc.contributor.icrauthor | Shepherd, Scott | |
dc.contributor.icrauthor | Shum, Ben | |
dc.contributor.icrauthor | Goicoechea, Maria | |
dc.contributor.icrauthor | Emmerich, Max | |
dc.contributor.icrauthor | Pallikonda, Husayn | |
dc.contributor.icrauthor | Furness, Andrew | |
icr.provenance | Deposited by Miss Maria Goicoechea on 2023-05-18. Deposit type is initial. No. of files: 1. Files: Late-stage metastatic melanoma.pdf | |