Multi-site clonality analysis uncovers pervasive heterogeneity across melanoma metastases

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Multi-site clonality analysis uncovers pervasive heterogeneity across melanoma metastases. / Rabbie, Roy; Ansari-pour, Naser; Cast, Oliver; Lau, Doreen; Scott, Francis; Welsh, Sarah J.; Parkinson, Christine; Khoja, Leila; Moore, Luiza; Tullett, Mark; Wong, Kim; Ferreira, Ingrid; Gómez, Julia M. Martínez; Levesque, Mitchell; Gallagher, Ferdia A.; Jiménez-sánchez, Alejandro; Riva, Laura; Miller, Martin L.; Allinson, Kieren; Campbell, Peter J.; Corrie, Pippa; Wedge, David C.; Adams, David J.

In: Nature Communications, Vol. 11, No. 1, 27.08.2020.

Research output: Contribution to journalArticlepeer-review

Harvard

Rabbie, R, Ansari-pour, N, Cast, O, Lau, D, Scott, F, Welsh, SJ, Parkinson, C, Khoja, L, Moore, L, Tullett, M, Wong, K, Ferreira, I, Gómez, JMM, Levesque, M, Gallagher, FA, Jiménez-sánchez, A, Riva, L, Miller, ML, Allinson, K, Campbell, PJ, Corrie, P, Wedge, DC & Adams, DJ 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

APA

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., ... Adams, D. J. (2020). Multi-site clonality analysis uncovers pervasive heterogeneity across melanoma metastases. Nature Communications, 11(1). https://doi.org/10.1038/s41467-020-18060-0

Vancouver

Author

Rabbie, Roy ; Ansari-pour, Naser ; Cast, Oliver ; Lau, Doreen ; Scott, Francis ; Welsh, Sarah J. ; Parkinson, Christine ; Khoja, Leila ; Moore, Luiza ; Tullett, Mark ; Wong, Kim ; Ferreira, Ingrid ; Gómez, Julia M. Martínez ; Levesque, Mitchell ; Gallagher, Ferdia A. ; Jiménez-sánchez, Alejandro ; Riva, Laura ; Miller, Martin L. ; Allinson, Kieren ; Campbell, Peter J. ; Corrie, Pippa ; Wedge, David C. ; Adams, David J. / Multi-site clonality analysis uncovers pervasive heterogeneity across melanoma metastases. In: Nature Communications. 2020 ; Vol. 11, No. 1.

Bibtex

@article{207362ab76024cfd9d07c912da58627d,
title = "Multi-site clonality analysis uncovers pervasive heterogeneity across melanoma metastases",
abstract = "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 na{\"i}ve 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.",
author = "Roy Rabbie and Naser Ansari-pour and Oliver Cast and Doreen Lau and Francis Scott and Welsh, {Sarah J.} and Christine Parkinson and Leila Khoja and Luiza Moore and Mark Tullett and Kim Wong and Ingrid Ferreira and G{\'o}mez, {Julia M. Mart{\'i}nez} and Mitchell Levesque and Gallagher, {Ferdia A.} and Alejandro Jim{\'e}nez-s{\'a}nchez and Laura Riva and Miller, {Martin L.} and Kieren Allinson and Campbell, {Peter J.} and Pippa Corrie and Wedge, {David C.} and Adams, {David J.}",
year = "2020",
month = aug,
day = "27",
doi = "10.1038/s41467-020-18060-0",
language = "English",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Springer",
number = "1",

}

RIS

TY - JOUR

T1 - Multi-site clonality analysis uncovers pervasive heterogeneity across melanoma metastases

AU - Rabbie, Roy

AU - Ansari-pour, Naser

AU - Cast, Oliver

AU - Lau, Doreen

AU - Scott, Francis

AU - Welsh, Sarah J.

AU - Parkinson, Christine

AU - Khoja, Leila

AU - Moore, Luiza

AU - Tullett, Mark

AU - Wong, Kim

AU - Ferreira, Ingrid

AU - Gómez, Julia M. Martínez

AU - Levesque, Mitchell

AU - Gallagher, Ferdia A.

AU - Jiménez-sánchez, Alejandro

AU - Riva, Laura

AU - Miller, Martin L.

AU - Allinson, Kieren

AU - Campbell, Peter J.

AU - Corrie, Pippa

AU - Wedge, David C.

AU - Adams, David J.

PY - 2020/8/27

Y1 - 2020/8/27

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-020-18060-0

DO - 10.1038/s41467-020-18060-0

M3 - Article

VL - 11

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

ER -