Multi-site clonality analysis uncovers pervasive heterogeneity across melanoma metastases

Autor: Luiza Moore, David J. Adams, Alejandro Jiménez-Sánchez, Mark Tullett, Laura Riva, Kim Wong, David C. Wedge, Martin L. Miller, Sarah J. Welsh, Doreen Lau, Christine Parkinson, Julia M. Martínez Gómez, Kieren Allinson, Pippa Corrie, Ingrid Ferreira, Francis Scott, Leila Khoja, Roy Rabbie, Naser Ansari-Pour, Peter J. Campbell, Mitchell P. Levesque, Ferdia A. Gallagher, Oliver Cast
Přispěvatelé: Rabbie, Roy [0000-0002-9195-5659], Cast, Oliver [0000-0002-5880-7726], Lau, Doreen [0000-0002-7623-2401], Moore, Luiza [0000-0001-5315-516X], Wong, Kim [0000-0002-0984-1477], Ferreira, Ingrid [0000-0002-4321-5250], Gallagher, Ferdia A. [0000-0003-4784-5230], Miller, Martin L. [0000-0003-3161-8690], Campbell, Peter J. [0000-0002-3921-0510], Wedge, David C. [0000-0002-7572-3196], Adams, David J. [0000-0001-9490-0306], Apollo - University of Cambridge Repository, Gallagher, Ferdia A [0000-0003-4784-5230], Miller, Martin L [0000-0003-3161-8690], Campbell, Peter J [0000-0002-3921-0510], Wedge, David C [0000-0002-7572-3196], Adams, David J [0000-0001-9490-0306]
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
Oncology
Skin Neoplasms
Microarrays
Biopsy
DNA Mutational Analysis
General Physics and Astronomy
02 engineering and technology
Disease
Somatic evolution in cancer
Metastasis
631/114/2397
Computational models
Prospective Studies
lcsh:Science
Melanoma
Skin
45/90
Multidisciplinary
Phylogenetic tree
medicine.diagnostic_test
article
49/39
021001 nanoscience & nanotechnology
631/67/322
0210 nano-technology
medicine.medical_specialty
Génétique moléculaire
Lineage (genetic)
Tumour heterogeneity
Science
45/22
45/23
Biology
631/67/1813/1634
631/67/2329
631/114/2407
General Biochemistry
Genetics and Molecular Biology
Clonal Evolution
Genetic Heterogeneity
03 medical and health sciences
Internal medicine
medicine
Humans
Aged
Whole Genome Sequencing
Genetic heterogeneity
General Chemistry
medicine.disease
Sciences humaines
030104 developmental biology
lcsh:Q
Zdroj: Nature communications, 11 (1
Nature Communications, Vol 11, Iss 1, Pp 1-12 (2020)
Nature Communications
Rabbie, R, Ansari-pour, N, Cast, O, Lau, D, Scott, F, Welsh, S J, Parkinson, C, Khoja, L, Moore, L, Tullett, M, Wong, K, Ferreira, I, Gómez, J M M, Levesque, M, Gallagher, F A, Jiménez-sánchez, A, Riva, L, Miller, M L, Allinson, K, Campbell, P J, Corrie, P, Wedge, D C & Adams, D J 2020, ' Multi-site clonality analysis uncovers pervasive heterogeneity across melanoma metastases ', Nature Communications, vol. 11, no. 1 . https://doi.org/10.1038/s41467-020-18060-0
DOI: 10.1038/s41467-020-18060-0
Popis: Metastatic melanoma carries a poor prognosis despite modern systemic therapies. Understanding the evolution of the disease could help inform patient management. Through whole-genome sequencing of 13 melanoma metastases sampled at autopsy from a treatment naïve patient and by leveraging the analytical power of multi-sample analyses, we reveal evidence of diversification among metastatic lineages. UV-induced mutations dominate the trunk, whereas APOBEC-associated mutations are found in the branches of the evolutionary tree. Multi-sample analyses from a further seven patients confirmed that lineage diversification was pervasive, representing an important mode of melanoma dissemination. Our analyses demonstrate that joint analysis of cancer cell fraction estimates across multiple metastases can uncover previously unrecognised levels of tumour heterogeneity and highlight the limitations of inferring heterogeneity from a single biopsy.
Metastatic melanoma is associated with a poor prognosis and understanding the genetic features of metastases may enable better treatment strategies. Here, the authors analyse multiple metastases from individual patients finding high levels of heterogeneity in metastases from different organs.
Databáze: OpenAIRE
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