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Article
The mutational landscape of normal human endometrial epithelium
All normal somatic cells are thought to acquire mutations, but understanding of the rates, patterns, causes and consequences of somatic mutations in normal cells is limited. The uterine endometrium adopts mult...
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Article
Open AccessCirculating tumor DNA in patients with colorectal adenomas: assessment of detectability and genetic heterogeneity
Improving early detection of colorectal cancer (CRC) is a key public health priority as adenomas and stage I cancer can be treated with minimally invasive procedures. Population screening strategies based on d...
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Article
Open AccessRecurrent rearrangements of FOS and FOSB define osteoblastoma
The transcription factor FOS has long been implicated in the pathogenesis of bone tumours, following the discovery that the viral homologue, v-fos, caused osteosarcoma in laboratory mice. However, mutations of FO...
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Article
Open AccessThe driver landscape of sporadic chordoma
Chordoma is a malignant, often incurable bone tumour showing notochordal differentiation. Here, we defined the somatic driver landscape of 104 cases of sporadic chordoma. We reveal somatic duplications of the ...
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Article
Open AccessRecurrent mutation of IGF signalling genes and distinct patterns of genomic rearrangement in osteosarcoma
Osteosarcoma is a primary malignancy of bone that affects children and adults. Here, we present the largest sequencing study of osteosarcoma to date, comprising 112 childhood and adult tumours encompassing all...
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Article
Open AccessMutational signatures of ionizing radiation in second malignancies
Ionizing radiation is a potent carcinogen, inducing cancer through DNA damage. The signatures of mutations arising in human tissues following in vivo exposure to ionizing radiation have not been documented. Here,...
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Article
Open AccessA comprehensive assessment of somatic mutation detection in cancer using whole-genome sequencing
As whole-genome sequencing for cancer genome analysis becomes a clinical tool, a full understanding of the variables affecting sequencing analysis output is required. Here using tumour-normal sample pairs from...
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Article
Combined hereditary and somatic mutations of replication error repair genes result in rapid onset of ultra-hypermutated cancers
Adam Shlien, Peter Campbell, Uri Tabori and colleagues report genome and exome sequencing of biallelic mismatch repair deficiency cancer samples from 12 children, including 10 high-grade gliomas. The hypermuta...
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Article
Genome sequencing of normal cells reveals developmental lineages and mutational processes
On the basis of whole-genome sequences of clonal lines derived from normal mouse tissues, variation in mutational patterns and load across different tissues are described and early embryonic cell divisions are...
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Article
Open AccessProcessed pseudogenes acquired somatically during cancer development
Cancer evolves by mutation, with somatic reactivation of retrotransposons being one such mutational process. Germline retrotransposition can cause processed pseudogenes, but whether this occurs somatically has...
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Article
Recurrent PTPRB and PLCG1 mutations in angiosarcoma
Peter Campbell and colleagues identify PLCG1 and PTPRB as new driver genes for angiosarcoma through whole-exome sequencing of tumor samples. They find somatic PTPRB mutations in 10 of 39 cases and PLCG1 mutations...
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Article
Correction: Corrigendum: Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone
Nat. Genet. 45, 1479–1482 (2013); published online 27 October 2013; corrected after print 6 February 2014 In the version of this article initially published, the name of author Victoria Goody was misspelled, a...
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Article
Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone
Adrienne Flanagan and colleagues identify distinct driver mutations in H3F3A and H3F3B in chondroblastoma and giant cell tumor of bone. The mutations occur in over 90% of tumors and exhibit a high degree of tumor...
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Article
Frequent mutation of the major cartilage collagen gene COL2A1 in chondrosarcoma
Andrew Futreal and colleagues identify the major cartilage collagen gene COL2A1 as a frequent target of somatic mutation in chondrosarcoma. The mutation patterns are consistent with selection for variants likely ...
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Article
Secretory meningiomas are defined by combined KLF4 K409Q and TRAF7 mutations
Meningiomas are among the most frequent intracranial tumors. The secretory variant of meningioma is characterized by glandular differentiation, formation of intracellular lumina and pseudopsammoma bodies, expr...
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Article
A common single-nucleotide variant in T is strongly associated with chordoma
Adrienne Flanagan and colleagues identify a common variant in the T gene associated with strong risk of chordoma, a rare malignant bone tumor. The risk variant alters an amino acid in the DNA-binding domain of th...
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Article
The landscape of cancer genes and mutational processes in breast cancer
A study of breast cancers shows that the number of somatic mutations in each varies markedly and is strongly correlated with age at diagnosis and cancer histological grade.
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Article
Mutations in the guanine nucleotide exchange factor gene IQSEC2 cause nonsyndromic intellectual disability
Cheryl Shoubridge and Jozef Gecz and colleagues report the identification of mutations in IQSEC2, a guanine nucleotide exchange factor for ARF GTPases, in individuals with non-syndromic intellectual disability.
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Article
Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes
A large survey for somatic mutations in clear cell renal cell carcinomas, the most common form of adult kidney cancer, shows that in addition to the known inactivating mutations in the VHL gene, recurrent mutatio...
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Article
Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer
Andrew Futreal and colleagues report inactivating somatic mutations in the histone lysine demethylase gene UTX in human cancers, including multiple myelomas, esophageal squamous carcinomas, renal clear cell carci...
