Volume 45 Issue 8, August 2013

Recent studies have identified recurrent mutations in SETBP1, the gene that encodes SET-binding protein 1, in several types of myeloid malignancies, including chronic myeloid and acute myeloid leukemias. The identified mutations frequently target the SKI-homologous domain, although the exact pathogenic mechanisms remain unknown.

Two recent large-scale sequencing studies have identified multiple genetic aberrations in pediatric low-grade gliomas. These findings offer substantial insights that may spur the development of new diagnostics and treatments for these cancers.

Two recent studies describe the largest molecular profiling analyses to date of clear-cell renal cell carcinoma (ccRCC) and report remarkably similar findings. The recurrent pathway alterations identified in these studies open new avenues for therapeutic advances in this chemotherapy- and radiation-resistant disease.

John Stamatoyannopoulos, John Mattick and colleagues use DNase I–hypersensitive site maps from 86 diverse cell types to identify a subset of exons that have DNase I hypersensitivity and are accompanied by 'phantom' signals in chromatin immunoprecipitation and sequencing (ChIP-seq) resulting from cross-linking with proximal promoter- or enhancer-bound factors.

Seishi Ogawa and colleagues report an integrated genomics analysis of more than 100 clear-cell renal carcinoma samples. They analyze whole genomes or exomes, RNA sequences and DNA methylation in ∼100 paired specimens and perform SNP array-based copy number analysis for 240 specimens. They identify new recurrently mutated pathways and new associations between DNA methylation, mutations, gene expression and copy number profiles.

Susan Slager and colleagues report a meta-analysis of genome-wide association studies for chronic lymphocytic leukemia (CLL). They identify nine loci newly associated with CLL.

David Page and colleagues report that entry into meiosis is not required for oocyte development, which goes against previous concepts that entry into meiosis initiated oocyte differentiation and development. They show that mice lacking Stra8 fail in premeiotic replication and meiotic prophase.

Magnus Nordborg and colleagues report sequencing of 180 Arabidopsis thaliana lines from Sweden. They characterize patterns of genetic variation and selection and provide a population resource that will be useful for association studies.

Mathieu Blanchette and colleagues report whole-genome sequencing of three Brassicaceae species, Leavenworthia alabamica, Sisymbrium irio and Aethionema arabicum. They include comparative genomic analysis with 6 additional crucifier genomes, identify and characterize over 90,000 conserved noncoding sequences and provide a map of functional noncoding regions in plant genomes.

Eric Boerwinkle and colleagues report whole-genome sequencing of a population-based sample of 962 individuals from three Cohorts for Heart and Aging Research in Genetic Epidemiology (CHARGE) studies. They analyze the genetic architecture of high-density lipoprotein cholesterol (HDL-C) levels and estimate that common variation contributes more to HDL-C heritability than rare variation.

Klaus Bønnelykke and colleagues report results of a genome-wide association study of allergic sensitization. They identify ten loci influencing this phenotype and provide insight into the shared genetic basis of allergic sensitization and atopic diseases.

David Hinds and colleagues report results of a genome-wide association meta-analysis of self-reported allergy. They identify 16 shared susceptibility loci for allergic traits, including 8 loci previously associated with asthma.

Verneri Anttila and colleagues report meta-analysis of 29 genome-wide association studies for migraine. They identify five loci newly associated with migraine, three of which are associated with specific subtypes of migraine with or without aura.

Ding Ma, Xing Xie, Yongyong Shi and colleagues report a genome-wide association study of cervical cancer in the Han Chinese population. They identify two new susceptibility lociat 4q12 and 17q12.

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 to impair normal collagen biosynthesis.

Stefan Pfister and the ICGC PedBrain Tumor Project report whole-genome sequencing of 96 pilocytic astrocytomas. They identify recurrent activating mutations in FGFR1 and PTPN11 and novel NTRK2 fusion genes.

Michael Zeschnigk and colleagues identify recurrent somatic mutations of EIF1AX and SF3B1 in uveal melanomas with disomy 3. The EIF1AX mutations specifically alter the N-terminal tail of the protein and were found exclusively in tumors lacking SF3B1 mutations.

Seiji Kojima and colleagues report whole-exome sequencing of 13 juvenile myelomonocytic leukemias. They identify RAS pathway mutations in 82 of the 92 total cases analyzed and mutations in SETBP1 or JAK3 in 16 cases.

Jaroslaw Maciejewski and colleagues report whole-exome sequencing of 20 cases of myeloid malignancies, with follow up of SETBP1 in 727 further cases of myeloid malignancies. They identify SETBP1 mutations in 52 cases (7.2%).

Andrew Hattersley and colleagues show that an in-frame deletion in POLD1 affecting the polymerase active site causes a multisystem disorder characterized by lipodystrophy, deafness and mandibular hypoplasia. This recurrent mutation abolishes DNA polymerase activity but only mildly impairs 3'- to 5'-exonuclease activity.

Soeren Lienkamp, Carsten Bergmann, Friedhelm Hildebrandt and colleagues show that mutations in ANKS6 cause nephronophthisis, a recessive cystic kidney disease. They further identify ANKS6 as a component of a protein module that includes INVS (NPHP2), NPHP3 and NEK8 (NPHP9).

Bin Han and colleagues report de novo assembly of the genome of a wild progenitor (Setaria viridis) of foxtail millet and low-pass resequencing of 916 diverse foxtail millet varieties. They identify 0.8 million common SNPs, construct a haplotype map of foxtail millet and perform genome-wide association studies on 47 agronomic traits.