Genomic landscape of platinum resistant and sensitive testicular cancers

Chey Loveday; Kevin Litchfield; Paula Z Proszek; Alex J Cornish; Flavia Santo; Max Levy; Geoff Macintyre; Amy Holryod; Peter Broderick; Darshna Dudakia; Barbara Benton; Maise Al Bakir; Crispin Hiley; Emily Grist; Charles Swanton; Robert Huddart; Tom Powles; Simon Chowdhury; Janet Shipley; Simon O'Connor; James D Brenton; Alison Reid; David Gonzalez de Castro; Richard S Houlston; Clare Turnbull

doi:10.1038/s41467-020-15768-x

Genomic landscape of platinum resistant and sensitive testicular cancers

Chey Loveday, Kevin Litchfield, Paula Z Proszek, Alex J Cornish, Flavia Santo, Max Levy, Geoff Macintyre, Amy Holryod, Peter Broderick, Darshna Dudakia, Barbara Benton, Maise Al Bakir, Crispin Hiley, Emily Grist, Charles Swanton, Robert Huddart, Tom Powles, Simon Chowdhury, Janet Shipley, Simon O'ConnorJames D Brenton, Alison Reid, David Gonzalez de Castro, Richard S Houlston, Clare Turnbull

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Abstract

While most testicular germ cell tumours (TGCTs) exhibit exquisite sensitivity to platinum chemotherapy, ~10% are platinum resistant. To gain insight into the underlying mechanisms, we undertake whole exome sequencing and copy number analysis in 40 tumours from 26 cases with platinum-resistant TGCT, and combine this with published genomic data on an additional 624 TGCTs. We integrate analyses for driver mutations, mutational burden, global, arm-level and focal copy number (CN) events, and SNV and CN signatures. Albeit preliminary and observational in nature, these analyses provide support for a possible mechanistic link between early driver mutations in RAS and KIT and the widespread copy number events by which TGCT is characterised.

Original language	English
Pages (from-to)	2189
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-15768-x
Publication status	Published - 04 May 2020

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Genomic landscape of platinum resistant and sensitive testicular cancers
Copyright 2020 the authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 1.02 MBLicence: CC BY

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Loveday, C., Litchfield, K., Proszek, P. Z., Cornish, A. J., Santo, F., Levy, M., Macintyre, G., Holryod, A., Broderick, P., Dudakia, D., Benton, B., Bakir, M. A., Hiley, C., Grist, E., Swanton, C., Huddart, R., Powles, T., Chowdhury, S., Shipley, J., ... Turnbull, C. (2020). Genomic landscape of platinum resistant and sensitive testicular cancers. Nature Communications, 11(1), 2189. https://doi.org/10.1038/s41467-020-15768-x

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title = "Genomic landscape of platinum resistant and sensitive testicular cancers",

abstract = "While most testicular germ cell tumours (TGCTs) exhibit exquisite sensitivity to platinum chemotherapy, ~10% are platinum resistant. To gain insight into the underlying mechanisms, we undertake whole exome sequencing and copy number analysis in 40 tumours from 26 cases with platinum-resistant TGCT, and combine this with published genomic data on an additional 624 TGCTs. We integrate analyses for driver mutations, mutational burden, global, arm-level and focal copy number (CN) events, and SNV and CN signatures. Albeit preliminary and observational in nature, these analyses provide support for a possible mechanistic link between early driver mutations in RAS and KIT and the widespread copy number events by which TGCT is characterised.",

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Loveday, C, Litchfield, K, Proszek, PZ, Cornish, AJ, Santo, F, Levy, M, Macintyre, G, Holryod, A, Broderick, P, Dudakia, D, Benton, B, Bakir, MA, Hiley, C, Grist, E, Swanton, C, Huddart, R, Powles, T, Chowdhury, S, Shipley, J, O'Connor, S, Brenton, JD, Reid, A, de Castro, DG, Houlston, RS & Turnbull, C 2020, 'Genomic landscape of platinum resistant and sensitive testicular cancers', Nature Communications, vol. 11, no. 1, pp. 2189. https://doi.org/10.1038/s41467-020-15768-x

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T1 - Genomic landscape of platinum resistant and sensitive testicular cancers

AU - Loveday, Chey

AU - Litchfield, Kevin

AU - Proszek, Paula Z

AU - Cornish, Alex J

AU - Santo, Flavia

AU - Levy, Max

AU - Macintyre, Geoff

AU - Holryod, Amy

AU - Broderick, Peter

AU - Dudakia, Darshna

AU - Benton, Barbara

AU - Bakir, Maise Al

AU - Hiley, Crispin

AU - Grist, Emily

AU - Swanton, Charles

AU - Huddart, Robert

AU - Powles, Tom

AU - Chowdhury, Simon

AU - Shipley, Janet

AU - O'Connor, Simon

AU - Brenton, James D

AU - Reid, Alison

AU - de Castro, David Gonzalez

AU - Houlston, Richard S

AU - Turnbull, Clare

PY - 2020/5/4

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AB - While most testicular germ cell tumours (TGCTs) exhibit exquisite sensitivity to platinum chemotherapy, ~10% are platinum resistant. To gain insight into the underlying mechanisms, we undertake whole exome sequencing and copy number analysis in 40 tumours from 26 cases with platinum-resistant TGCT, and combine this with published genomic data on an additional 624 TGCTs. We integrate analyses for driver mutations, mutational burden, global, arm-level and focal copy number (CN) events, and SNV and CN signatures. Albeit preliminary and observational in nature, these analyses provide support for a possible mechanistic link between early driver mutations in RAS and KIT and the widespread copy number events by which TGCT is characterised.

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DO - 10.1038/s41467-020-15768-x

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SN - 2041-1723

VL - 11

SP - 2189

JO - Nature Communications

JF - Nature Communications

IS - 1

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Genomic landscape of platinum resistant and sensitive testicular cancers

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