Multi-site clonality analysis uncovers pervasive heterogeneity across melanoma metastases

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

doi:10.1038/s41467-020-18060-0

Multi-site clonality analysis uncovers pervasive heterogeneity across melanoma metastases

Roy Rabbie, Naser Ansari-pour, Oliver Cast, Doreen Lau, Francis Scott, Sarah J. Welsh, Christine Parkinson, Leila Khoja, Luiza Moore, Mark Tullett, Kim Wong, Ingrid Ferreira, Julia M. Martínez Gómez, Mitchell Levesque, Ferdia A. Gallagher, Alejandro Jiménez-sánchez, Laura Riva, Martin L. Miller, Kieren Allinson, Peter J. CampbellPippa Corrie, David C. Wedge, David J. Adams

Immunology and Immunotherapy

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

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 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.

Original language	English
Article number	4306
Journal	Nature Communications
Volume	11
Issue number	1
Early online date	27 Jul 2020
DOIs	https://doi.org/10.1038/s41467-020-18060-0
Publication status	Published - 27 Aug 2020

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http://www.nature.com/articles/s41467-020-18060-0

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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), Article 4306. https://doi.org/10.1038/s41467-020-18060-0

@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.}",

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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, 4306. https://doi.org/10.1038/s41467-020-18060-0

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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.

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VL - 11

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 4306

ER -

Multi-site clonality analysis uncovers pervasive heterogeneity across melanoma metastases

Abstract

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