1 SUMMARYThe advance of personalized cancer medicine requires the accurate identification of the mutations driving each patient's tumor. However, to date, we have only been able to obtain partial insights into the contribution of genomic events to tumor development. Here, we design a comprehensive approach to identify the driver mutations in each patient's tumor and obtain a whole-genome panorama of driver events across more than 2,500 tumors from 37 types of cancer. This panorama includes coding and non-coding point mutations, copy number alterations and other genomic rearrangements of somatic origin, and potentially predisposing germline variants. We demonstrate that genomic events are at the root of virtually all tumors, with each carrying on average 4.6 driver events. Most individual tumors harbor a unique combination of drivers, and we uncover the most frequent co-occurring driver events. Half of all cancer genes are affected by several types of driver mutations. In summary, the panorama described here provides answers to fundamental questions in cancer genomics and bridges the gap between cancer genomics and personalized cancer medicine.Tumors arise from genomic mutations, often referred to as 'drivers', that confer proliferative advantage to a The characterization of more than 2,500 tumors by the International Cancer Genomics Consortium (ICGC) and The Cancer Genome Atlas (TCGA) under the Pan-Cancer Analysis of Whole Genomes 2 (PCAWG) 16 initiative provides an unprecedented opportunity to obtain a comprehensive whole-genome view of driver events in cancer. Here, we set the goal of identifying all driver events (somatic point mutations, SCNAs, SGRs, and potentially predisposing germline variants) across the whole genome of each tumor in the PCAWG cohort. We call this list of driver events the per-patient panorama of driver mutations (or simply panorama). To obtain it, we designed an incremental approach ( Fig. 1a; Methods and Suppl. Notes 1 and 2)that exploits the power of this cohort to discover novel drivers, both coding and non-coding, and the knowledge accumulated through decades of cancer genetics research 2 . We found driver mutations in virtually all tumors, thereby providing definitive evidence of the oft-quoted maxim that cancer is fundamentally a genomics disease. We also demonstrated the presence of a small number of driver mutations in each tumor -4.6 on average, a number that is relatively stable regardless of of the variability in mutational burden. While the contribution of somatic point mutations and SVs to tumorigenesis across cancer types differs, their relative proportions across the entire cohort are very similar. We found that most individual tumors harbor a unique combination of driver mutations, and we uncovered the most frequently co-occurring driver events.Some of these combinations may have a synergistic effect in the emergence of cancer, as in the cases of somatic point mutations of KRAS and SMAD4 in pancreatic adenocarcinomas (Panc-AdenoCA) and DAXX and MEN1 across pancreatic ...
Sexually dimorphic glands often release sexual pheromones both in vertebrates and invertebrates. Species of Laniatores (Arachnida, Opiliones) seem to depend on chemical communication but few studies have addressed this topic. In this study, we review the literature for the Phalangida and present new data for 23 species of Laniatores. In 16 taxa, we found previously undescribed sexually dimorphic glandular openings on the femur, patella, metatarsus, and tarsus of legs I and metatarsus of legs III and IV. For the other species, we provide scanning electron micrographs of previously undescribed sexually dimorphic setae and pegs located on swollen regions of the legs. We also list additional species in which males have swollen regions on the legs, including the tibia, metatarsus, and tarsus of legs I, trochanter and tibia of legs II, femur, metatarsus, and tarsus of legs III, and metatarsus and tarsus of legs IV. The function and biological role of the secretions released by these glands are discussed.
Triaenonychidae Sørensen in L. Koch, 1886 is a large family of Opiliones with ~480 described species broadly distributed across temperate forests in the Southern Hemisphere. However, it remains poorly understood taxonomically, as no comprehensive phylogenetic work has ever been undertaken. In this study we capitalise on samples largely collected by us during the last two decades and use Sanger DNA-sequencing techniques to produce a large phylogenetic tree with 300 triaenonychid terminals representing nearly 50% of triaenonychid genera and including representatives from all the major geographic areas from which they are known. Phylogenetic analyses using maximum likelihood and Bayesian inference methods recover the family as diphyletic, placing Lomanella Pocock, 1903 as the sister group to the New Zealand endemic family Synthetonychiidae Forster, 1954. With the exception of the Laurasian representatives of the family, all landmasses contain non-monophyletic assemblages of taxa. To determine whether this non-monophyly was the result of Gondwanan vicariance, ancient cladogenesis due to habitat regionalisation, or more recent over-water dispersal, we inferred divergence times. We found that most divergence times between landmasses predate Gondwanan breakup, though there has been at least one instance of transoceanic dispersal – to New Caledonia. In all, we identify multiple places in the phylogeny where taxonomic revision is needed, and transfer Lomanella outside of Triaenonychidae in order to maintain monophyly of the family.
Cavernicolous species that exhibit a high degree of troglomorphism often provide some of the most intriguing evolutionary riddles. For such taxa, the correct systematic arrangement is difficult to determine and becomes problematic when based solely on highly convergent external morphological characters, leading to exaggerated support of spurious relationships. For the arachnid order Opiliones, examination of male genitalia morphology often aids in determining the family to which a particular taxon belongs. However, many taxa described prior to the 1990s lack detailed descriptions or drawings of this important character and, for highly‐derived species, it is may still be necessary to seek support from additional sources of characters (e.g. molecular data) to accurately assess systematic placement. The enigmatic species Stygnomma pecki Goodnight & Goodnight, from a cave in Belize proved to be especially difficult to place based on morphological characters alone. Thus, using a previously published dataset for laniatorean harvestmen, we carried out a robust phylogenetic analysis aiming to determine the evolutionary relationship of this Neotropical troglomophic species. Informed by the results of the molecular phylogenetic analysis of 88 terminals representing Laniatores, we describe Jarmilana gen. nov. and provide a redescription of the type species Jarmilana pecki (Goodnight & Goodnight, ) comb. nov. Morphological evidence, including male genitalia morphology, supports the inclusion of J. pecki in the family Pyramidopidae. This represents the first record for the family Pyramidopidae in the New World, raising the question of whether this represents transoceanic dispersal or a relict of an ancient widespread tropical Gondwanan distribution.
A new troglobitic harvestman, Relictopiolus galadriel gen. nov et sp. nov., is described from Olhos d’Água cave, Itacarambi, Minas Gerais State, Brazil. Morphological characters, including male genitalia and exomorphology, suggest that this species belongs to the family Kimulidae, and it appears to share the greatest similarities with Tegipiolus pachypus. Bayesian inference analyses of a molecular dataset strongly support the inclusion of this species in Kimulidae and confirm the hypothesized sister-group relationship between R. galadriel and T. pachypus. A time calibrated phylogeny indicates that these sister-taxa diverged from a common ancestor approximately 40 Mya, during the Paleogene. The current range of Kimulidae illustrates a remarkable disjunct distribution, and leads us to hypothesize that the ancestral distribution of Kimulidae was once much more widespread across eastern Brazil. This may be attributed to the Eocene radiation associated with the warming (and humidifying) events in the Cenozoic when the best conditions for evergreen tropical vegetation in South America were established and followed by the extinction of kimulid epigean populations together with the retraction of rain forests during the Oligocene to Miocene cooling. The discovery of this relictual troglobite indicates that the Olhos d’Água cave was a stable refugium for this ancient lineage of kimulids and acted as a "museum" of biodiversity. Our findings, considered collectively with the diverse troglofauna of the Olhos d’Água cave, highlight it as one of the most important hotspots of troglobite diversity and endemism in the Neotropics. Given the ecological stresses on this habitat, the cavernicolous fauna are at risk of extinction and we emphasize the urgent need for appropriate conservation actions. Finally, we propose the transfer of Acanthominua, Euminua, Euminuoides and Pseudominua from Kimulidae to Zalmoxidae, resulting in two new synonymies and 13 new combinations.
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