title: Whole-exome sequencing reveals the mutational spectrum of testicular germ cell tumours.
abstract: 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.
authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK.
authors.forename: Kevin
authors.initials: K
authors.lastname: Litchfield
authors.affiliation: Divisions of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK.
authors.forename: Brenda
authors.initials: B
authors.lastname: Summersgill
authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK.
authors.forename: Shawn
authors.initials: S
authors.lastname: Yost
authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK.
authors.forename: Razvan
authors.initials: R
authors.lastname: Sultana
authors.affiliation: 1] Division of Genetics and Epidemiology, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK [2] Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, F-75019, Paris, France.
authors.forename: Karim
authors.initials: K
authors.lastname: Labreche
authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK.
authors.forename: Darshna
authors.initials: D
authors.lastname: Dudakia
authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK.
authors.forename: Anthony
authors.initials: A
authors.lastname: Renwick
authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK.
authors.forename: Sheila
authors.initials: S
authors.lastname: Seal
authors.affiliation: Divisions of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK.
authors.forename: Reem
authors.initials: R
authors.lastname: Al-Saadi
authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Broderick
authors.affiliation: The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK.
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Turner
authors.affiliation: Division of Genetics and Epidemiology, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
authors.affiliation: Academic Radiotherapy Unit, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Huddart
authors.affiliation: Divisions of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK.
authors.forename: Janet
authors.initials: J
authors.lastname: Shipley
authors.affiliation: 1] Division of Genetics and Epidemiology, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK [2] William Harvey Research Institute, Queen Mary University London, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: Clare
authors.initials: C
authors.lastname: Turnbull
mesh_terms: D000328:Adult; D002869:Chromosome Aberrations; D002881:Chromosomes, Human, Pair 12; D002945:Cisplatin / Q000737:chemistry; D015331:Cohort Studies; D004252:DNA Mutational Analysis / Q000379:methods*; D004268:DNA-Binding Proteins / Q000378:metabolism; D018450:Disease Progression; D059472:Exome; D018628:Gene Dosage; D016147:Genes, Tumor Suppressor; D006801:Humans; D007378:Interleukins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics* / Q000601:surgery; D020641:Polymorphism, Single Nucleotide; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D018239:Seminoma / Q000235:genetics; D013090:Spermatocytes / Q000166:cytology; D013736:Testicular Neoplasms / Q000235:genetics* / Q000601:surgery; D000099180:Interleukin-24
chemical_list: D002945:Cisplatin; D004268:DNA-Binding Proteins; D007378:Interleukins; D019009:Proto-Oncogene Proteins c-kit; D000099180:Interleukin-24; C113187:XRCC2 protein, human