Whole-exome sequencing reveals the mutational spectrum of testicular germ cell tumours.
View/ Open
Date
2015-01-22ICR Author
Author
Litchfield, K
Summersgill, B
Yost, S
Sultana, R
Labreche, K
Dudakia, D
Renwick, A
Seal, S
Al-Saadi, R
Broderick, P
Turner, NC
Houlston, RS
Huddart, R
Shipley, J
Turnbull, C
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Spermatocytes
Chromosomes, Human, Pair 12
Humans
Neoplasms, Germ Cell and Embryonal
Seminoma
Testicular Neoplasms
Chromosome Aberrations
Disease Progression
Cisplatin
DNA-Binding Proteins
Interleukins
Cohort Studies
DNA Mutational Analysis
Gene Dosage
Mutation
Polymorphism, Single Nucleotide
Genes, Tumor Suppressor
Adult
Middle Aged
Male
Proto-Oncogene Proteins c-kit
Exome
Research team
Molecular Oncology
Cancer Genomics
Molecular & Population Genetics
Sarcoma Molecular Pathology
Clinical Academic Radiotherapy (Huddart)
Language
eng
Date accepted
2014-11-25
License start date
2015-01-22
Citation
Nature communications, 2015, 6 pp. 5973 - ?
Publisher
NATURE PUBLISHING GROUP