Articles in 2015

Laurent Frantz and colleagues report an analysis of 103 whole genomes from European and Asian wild boars and domestic pigs. They find evidence in support of a complex domestication model with gene flow from wild populations counteracted by recurrent artificial selection for traits important for domestication.

Wei Li, Qianben Wang and colleagues analyze genome-wide epigenetic patterns in tumor and normal tissues and find that broad H3K4me3 peaks are associated with increased transcription elongation and are enriched at tumor-suppressor genes. They demonstrate that this epigenetic mark may be used to identify new candidate tumor-suppressor genes.

Roderic Guigó, Montserrat Corominas and colleagues find that histone marks associated with active chromatin are absent from genes with high expression during specific developmental stages in both Drosophila melanogaster and Caenorhabditis elegans. They observe similar patterns for genes with high levels of transcriptional variation across mammalian tissues and cell types.

Isabelle Plo, Christine Bellanné-Chantelot, William Vainchenker and colleagues report a 700-kb germline duplication including the ATG2B and GSKIP genes in four related families with myeloid malignancy predisposition. Using induced pluripotent stem cells and primary cells, they demonstrate that ATG2B and GSKIP enhance hematopoietic progenitor differentiation.

Tatsuhiro Shibata and colleagues molecularly characterize 260 biliary tract cancer samples by a combination of exome and transcriptome sequencing. They find genomic alterations that could potentially be therapeutic targets.

Guy Sauvageau, Josée Hébert and colleagues analyze exomes and transcriptomes in MLL-rearranged acute myeloid leukemias. They find frequent RAS pathway mutations, which sensitize leukemias to MEK and receptor tyrosine kinase inhibitors.

Matthew Law, Mark Iles and colleagues report the results of a large-scale genome-wide meta-analysis of cutaneous malignant melanoma. They confirm previously reported association signals and identify five new susceptibility loci, with associated variants mapping within putative melanocyte regulatory elements.

Steve Brown and colleagues report an analysis of 20 phenotyping tests, including 413 data parameters, across 449 mutant mouse alleles. They identify widespread pleiotropy and assign putative functions to genes that lacked previous phenotypic annotation.

Jean-Pierre Bourquin, Martin Stanulla and colleagues report whole genome, whole exome and transcriptome sequencing of TCF3-HLF fusion–positive acute lymphoblastic leukemia. Drug response profiling in patient-derived xenografts identified sensitivity to the BCL2-specific inhibitor ABT-199 (venetoclax) as a new option for treating this fatal disease.

Ruth Halaban, Michael Krauthammer and colleagues report exome sequencing of 213 melanomas and identify a distinct co-mutation pattern of NF1 with known RASopathy genes. They identify novel melanoma mutations in several RASopathy genes and suggest that mutations in these genes may enhance the pathogenicity of NF1 mutation.

Richard Lifton and colleagues report a genomic analysis of cutaneous T cell lymphoma (CTCL). Their results implicate several pathways in CTCL pathogenesis, including genes involved in T cell activation and apoptosis, NF-κB signaling, chromatin remodeling and DNA damage response.

Adam Bass, Gad Getz, Scott Carter and colleagues report the whole-exome sequences of 25 pairs of esophageal adenocarcinoma and Barrett's esophagus. They identify two pathways by which Barrett's esophagus can develop into esophageal adenocarcinoma.

Rebecca Fitzgerald and colleagues report whole-genome sequence analyses of 23 paired samples of Barrett's esophagus and esophageal adenocarcinoma. Their analyses of the clonal architecture of these lesions shows that copy number increases and heterogeneity persists during development of esophageal adenocarcinoma.

Rinse Weersma, Carl Anderson and colleagues report the results of a trans-ancestry association study of inflammatory bowel disease. They implicate 38 new susceptibility loci, and show that the variance explained by each IBD risk locus is consistent across diverse ancestries, with a few notable exceptions.

Soumya Raychaudhuri and colleagues present a detailed analysis of the association between the HLA region and type 1 diabetes risk. They find that variants at three amino acid positions in HLA-DQβ1 and HLA-DRβ1 account for a large fraction of the association signal, acting through a combination of additive and interaction effects.

John Maris, Jan Molenaar, Gudrun Schleiermacher and colleagues performed whole-genome sequencing of 23 paired diagnostic and relapsed neuroblastomas, showing enrichment for mutations in the RAS-MAPK signaling pathway. These mutations render neuroblastoma cell lines susceptible to MEK inhibition.

Alexander Schramm, Johannes Schulte and colleagues characterize 16 paired samples from patients with neuroblastoma at diagnosis and relapse using whole-exome sequencing, mRNA expression profiling, array CGH and DNA methylation analysis. Their data show the frequency, identity and evolution of genetic alterations in neuroblastoma.

Richard Gilbertson and colleagues report an in vivo screen of 84 candidate oncogenes and 39 candidate tumor-suppressor genes in ependymoma mouse models. The validated targets are involved in vesicle trafficking, DNA modification and cholesterol biosynthesis.

Simon Gayther and colleagues report 3 new risk variants for mucinous ovarian carcinoma (MOC) on the basis of an analysis of 1,644 MOC cases and 21,693 controls. They confirm an eQTL association between the HOXD9 promoter and risk SNPs at 2q31.1 using chromosome conformation capture analysis and show that HOXD9 overexpression associates with neoplastic transformation.

José Martín-Subero and colleagues report the whole-genome bisulfite sequencing of ten blood cell subpopulations representing the cellular stages during B cell differentiation. They find that early stages are characterized by enhancer demethylation and that neoplasms derived from B cell lineages undergo methylation changes in regions with dynamic methylation during normal differentiation.