Whole-exome sequencing reveals the mutational spectrum of testicular germ cell tumours

Testicular germ cell tumours (TGCTs) are the most common cancer in young men. Here we perform whole-exome sequencing (WES) of 42 TGCTs to comprehensively study the cancer's mutational profile. The mutation rate is uniformly low in all of the tumours (mean 0.5 mutations per Mb) as compared with...

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Main Authors:	Litchfield, Kevin, Summersgill, Brenda, Yost, Shawn, Sultana, Razvan, Labreche, Karim, Dudakia, Darshna, Renwick, Anthony, Seal, Sheila, Al-Saadi, Reem, Broderick, Peter, Turner, Nicholas C., Houlston, Richard S., Huddart, Robert, Shipley, Janet, Turnbull, Clare
Format:	Online
Language:	English
Published:	Nature Publishing Group 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338546/

id	pubmed-4338546
recordtype	oai_dc
spelling	pubmed-43385462015-07-22 Whole-exome sequencing reveals the mutational spectrum of testicular germ cell tumours Litchfield, Kevin Summersgill, Brenda Yost, Shawn Sultana, Razvan Labreche, Karim Dudakia, Darshna Renwick, Anthony Seal, Sheila Al-Saadi, Reem Broderick, Peter Turner, Nicholas C. Houlston, Richard S. Huddart, Robert Shipley, Janet Turnbull, Clare Article Testicular germ cell tumours (TGCTs) are the most common cancer in young men. Here we perform whole-exome sequencing (WES) of 42 TGCTs to comprehensively study the cancer's mutational profile. The mutation rate is uniformly low in all of the tumours (mean 0.5 mutations per Mb) as compared with common cancers, consistent with the embryological origin of TGCT. In addition to expected copy number gain of chromosome 12p and mutation of KIT, we identify recurrent mutations in the tumour suppressor gene CDC27 (11.9%). Copy number analysis reveals recurring amplification of the spermatocyte development gene FSIP2 (15.3%) and a 0.4 Mb region at Xq28 (15.3%). Two treatment-refractory patients are shown to harbour XRCC2 mutations, a gene strongly implicated in defining cisplatin resistance. Our findings provide further insights into genes involved in the development and progression of TGCT. Nature Publishing Group 2015-01-22 /pmc/articles/PMC4338546/ /pubmed/25609015 http://dx.doi.org/10.1038/ncomms6973 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Litchfield, Kevin Summersgill, Brenda Yost, Shawn Sultana, Razvan Labreche, Karim Dudakia, Darshna Renwick, Anthony Seal, Sheila Al-Saadi, Reem Broderick, Peter Turner, Nicholas C. Houlston, Richard S. Huddart, Robert Shipley, Janet Turnbull, Clare
spellingShingle	Litchfield, Kevin Summersgill, Brenda Yost, Shawn Sultana, Razvan Labreche, Karim Dudakia, Darshna Renwick, Anthony Seal, Sheila Al-Saadi, Reem Broderick, Peter Turner, Nicholas C. Houlston, Richard S. Huddart, Robert Shipley, Janet Turnbull, Clare Whole-exome sequencing reveals the mutational spectrum of testicular germ cell tumours
author_facet	Litchfield, Kevin Summersgill, Brenda Yost, Shawn Sultana, Razvan Labreche, Karim Dudakia, Darshna Renwick, Anthony Seal, Sheila Al-Saadi, Reem Broderick, Peter Turner, Nicholas C. Houlston, Richard S. Huddart, Robert Shipley, Janet Turnbull, Clare
author_sort	Litchfield, Kevin
title	Whole-exome sequencing reveals the mutational spectrum of testicular germ cell tumours
title_short	Whole-exome sequencing reveals the mutational spectrum of testicular germ cell tumours
title_full	Whole-exome sequencing reveals the mutational spectrum of testicular germ cell tumours
title_fullStr	Whole-exome sequencing reveals the mutational spectrum of testicular germ cell tumours
title_full_unstemmed	Whole-exome sequencing reveals the mutational spectrum of testicular germ cell tumours
title_sort	whole-exome sequencing reveals the mutational spectrum of testicular germ cell tumours
description	Testicular germ cell tumours (TGCTs) are the most common cancer in young men. Here we perform whole-exome sequencing (WES) of 42 TGCTs to comprehensively study the cancer's mutational profile. The mutation rate is uniformly low in all of the tumours (mean 0.5 mutations per Mb) as compared with common cancers, consistent with the embryological origin of TGCT. In addition to expected copy number gain of chromosome 12p and mutation of KIT, we identify recurrent mutations in the tumour suppressor gene CDC27 (11.9%). Copy number analysis reveals recurring amplification of the spermatocyte development gene FSIP2 (15.3%) and a 0.4 Mb region at Xq28 (15.3%). Two treatment-refractory patients are shown to harbour XRCC2 mutations, a gene strongly implicated in defining cisplatin resistance. Our findings provide further insights into genes involved in the development and progression of TGCT.
publisher	Nature Publishing Group
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338546/
_version_	1613191894433529856

Whole-exome sequencing reveals the mutational spectrum of testicular germ cell tumours

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