Identification of novel mutational drivers reveals oncogene dependencies in multiple myeloma.

Understanding the profile of oncogene and tumor suppressor gene mutations with their interactions and impact on the prognosis of multiple myeloma (MM) can improve the definition of disease subsets and identify pathways important in disease pathobiology. Using integrated genomics of 1273 newly diagnosed patients with MM, we identified 63 driver genes, some of which are novel, including IDH1, IDH2, HUWE1, KLHL6, and PTPN11 Oncogene mutations are significantly more clonal than tumor suppressor mutations, indicating they may exert a bigger selective pressure. Patients with more driver gene abnormalities are associated with worse outcomes, as are identified mechanisms of genomic instability. Oncogenic dependencies were identified between mutations in driver genes, common regions of copy number change, and primary translocation and hyperdiploidy events. These dependencies included associations with t(4;14) and mutations in FGFR3, DIS3, and PRKD2; t(11;14) with mutations in CCND1 and IRF4; t(14;16) with mutations in MAF, BRAF, DIS3, and ATM; and hyperdiploidy with gain 11q, mutations in FAM46C, and MYC rearrangements. These associations indicate that the genomic landscape of myeloma is predetermined by the primary events upon which further dependencies are built, giving rise to a nonrandom accumulation of genetic hits. Understanding these dependencies may elucidate potential evolutionary patterns and lead to better treatment regimens.

Genome sequence of Ensifer arboris strain LMG 14919(T); a microsymbiont of the legume Prosopis chilensis growing in Kosti, Sudan.

Ensifer arboris LMG 14919(T) is an aerobic, motile, Gram-negative, non-spore-forming rod that can exist as a soil saprophyte or as a legume microsymbiont of several species of legume trees. LMG 14919(T) was isolated in 1987 from a nodule recovered from the roots of the tree Prosopis chilensis growing in Kosti, Sudan. LMG 14919(T) is highly effective at fixing nitrogen with P. chilensis (Chilean mesquite) and Acacia senegal (gum Arabic tree or gum acacia). LMG 14919(T) does not nodulate the tree Leucena leucocephala, nor the herbaceous species Macroptilium atropurpureum, Trifolium pratense, Medicago sativa, Lotus corniculatus and Galega orientalis. Here we describe the features of E. arboris LMG 14919(T), together with genome sequence information and its annotation. The 6,850,303 bp high-quality-draft genome is arranged into 7 scaffolds of 12 contigs containing 6,461 protein-coding genes and 84 RNA-only encoding genes, and is one of 100 rhizobial genomes sequenced as part of the DOE Joint Genome Institute 2010 Genomic Encyclopedia for Bacteria and Archaea-Root Nodule Bacteria (GEBA-RNB) project.