Articles in 2014

André Oliveira and colleagues identify a recurrent translocation in biphenotypic sinonasal sarcomas generating a PAX3-MAML3 fusion gene. The resulting protein is a potent transcriptional activator of PAX3 response elements and is associated with aberrant expression of genes involved in neuroectodermal and myogenic differentiation.

Stephen Scherer and colleagues report an inverse relationship between exon transcription levels in the developing brain and the burden of rare missense mutations. Using these data, they develop a contingency index that identifies critical exons harboring deleterious de novo mutations that are enriched in individuals with ASD relative to their unaffected siblings.

Robert West, Jonathan Pollack and colleagues identify mutations in either the Hedgehog pathway gene SMO or the MAPK gene BRAF in 24 of the 28 ameloblastoma samples studied. They found 9 of 11 SMO mutations were found in maxillary ameloblastomas, whereas 9 of 13 BRAF mutations were found in mandibular cases.

Wei Zheng and colleagues report the results of a large-scale genome-wide association study of colorectal cancer in East Asians. They identify six new susceptibility loci, including variants near TCF7L2 and TGFB1.

Yu-Xian Zhu, Jun Wang, Shuxun Yu and colleagues report sequencing and assembly of the genome of cultivated cotton, Gossypium arboreum. Comparison with the Gossypium raimondii genome sequence provides insights into genome evolution and speciation, and identifies two shared whole-genome duplication events occurring before the speciation event around 2–13 million years ago.

Suet Yi Leung, Mao Mao and colleagues report whole-genome sequencing of 100 gastric cancers and DNA copy number, gene expression and methylation profiling of these tumors. They identify new recurrently mutated genes and find mutation of RHOA in 14% of diffuse-type gastric cancers.

Nissim Benvenisty and colleagues use induced pluripotent stem cells (iPSCs) derived from individuals with Prader-Willi syndrome (PWS) to model PWS in vitro. By comparison to parthenogenetic human iPSCs, they find that the PWS-associated noncoding RNA IPW regulates maternally expressed genes at the DLK1-DIO3 imprinted region through its effect on H3K9me3 histone marks in that region.

Nicole Soranzo, Tim Spector, Gabi Kastenmüller and colleagues report a large-scale analysis of genetic variants influencing human blood metabolite levels. They identify genome-wide significant associations at 145 loci, providing a framework for exploring relationships between genetic variation, metabolism and complex disease.

Shumpei Ishikawa and colleagues report the identification of recurrent gain-of-function mutations in RHOA in diffuse-type gastric carcinomas.

Marc Ladanyi and colleagues identify a recurrent somatic mutation in MYOD1 in a subset of rhabdomyosarcomas with poor outcome. The mutation alters the DNA binding and transactivation properties of MYOD1 and promotes a switch from differentiation to proliferation.

Timothy Chan and colleagues show that the PARK2 tumor suppressor is a master regulator of G1 and S phase cyclins and is critical for proper cell cycle regulation. PARK2 genetic alterations are common across many human cancers as well as in hereditary Parkinson's disease.

Jonathan Fletcher and colleagues describe highly recurrent deletions of the large muscular dystrophy–associated gene DMD in gastrointestinal stromal tumors, rhabdomyosarcomas and leiomyosarcomas, all cancers with muscle differentiation. Re-expression of DMD in these tumor cells inhibits aspects of their metastatic phenotypes.

Many inherited human DNA repair deficiency syndromes involve pronounced neurological dysfunction, although the DNA lesions responsible are generally unknown. A new study shows that the phosphodiesterase TDP2 has a key role in protecting the nervous system by preventing DNA breaks induced by aberrant topoisomerase II activity.

Pediatric diffuse gliomas are rare but aggressive brain tumors for which effective therapies are unavailable. New studies identify recurrent mutations of the ACVR1 gene in these tumors, identify molecular subtypes and highlight differences between gliomas affecting children and adults.

Francis Collins, director of the US National Institutes of Health, recently highlighted in Nature the need to identify and correct systematic problems in biomedical research. One such effort, the Stanford Meta-Research Innovation Center, will monitor the practice of research and suggest policies for improvement. We commend this initiative that supports our commitment to publishing scientifically rigorous research.