High Mutability of the Tumor Suppressor Genes RASSF1 and RBSP3 (CTDSPL) in Cancer

BACKGROUND:Many different genetic alterations are observed in cancer cells. Individual cancer genes display point mutations such as base changes, insertions and deletions that initiate and promote cancer growth and spread. Somatic hypermutation is a powerful mechanism for generation of different mutations. It was shown previously that somatic hypermutability of proto-oncogenes can induce development of lymphomas. METHODOLOGY/PRINCIPAL FINDINGS:We found an exceptionally high incidence of single-base mutations in the tumor suppressor genes RASSF1 and RBSP3 (CTDSPL) both located in 3p21.3 regions, LUCA and AP20 respectively. These regions contain clusters of tumor suppressor genes involved in multiple cancer types such as lung, kidney, breast, cervical, head and neck, nasopharyngeal, prostate and other carcinomas. Altogether in 144 sequenced RASSF1A clones (exons 1-2), 129 mutations were detected (mutation frequency, MF = 0.23 per 100 bp) and in 98 clones of exons 3-5 we found 146 mutations (MF = 0.29). In 85 sequenced RBSP3 clones, 89 mutations were found (MF = 0.10). The mutations were not cytidine-specific, as would be expected from alterations generated by AID/APOBEC family enzymes, and appeared de novo during cell proliferation. They diminished the ability of corresponding transgenes to suppress cell and tumor growth implying a loss of function. These high levels of somatic mutations were found both in cancer biopsies and cancer cell lines. CONCLUSIONS/SIGNIFICANCE:This is the first report of high frequencies of somatic mutations in RASSF1 and RBSP3 in different cancers suggesting it may underlay the mutator phenotype of cancer. Somatic hypermutations in tumor suppressor genes involved in major human malignancies offer a novel insight in cancer development, progression and spread

A taxonomic backbone for the global synthesis of species diversity in the angiosperm order Caryophyllales

The Caryophyllales constitute a major lineage of flowering plants with approximately 12500 species in 39 families. A taxonomic backbone at the genus level is provided that reflects the current state of knowledge and accepts 749 genera for the order. A detailed review of the literature of the past two decades shows that enormous progress has been made in understanding overall phylogenetic relationships in Caryophyllales. The process of re-circumscribing families in order to be monophyletic appears to be largely complete and has led to the recognition of eight new families (Anacampserotaceae, Kewaceae, Limeaceae, Lophiocarpaceae, Macarthuriaceae, Microteaceae, Montiaceae and Talinaceae), while the phylogenetic evaluation of generic concepts is still well underway. As a result of this, the number of genera has increased by more than ten percent in comparison to the last complete treatments in the Families and genera of vascular plants” series. A checklist with all currently accepted genus names in Caryophyllales, as well as nomenclatural references, type names and synonymy is presented. Notes indicate how extensively the respective genera have been studied in a phylogenetic context. The most diverse families at the generic level are Cactaceae and Aizoaceae, but 28 families comprise only one to six genera. This synopsis represents a first step towards the aim of creating a global synthesis of the species diversity in the angiosperm order Caryophyllales integrating the work of numerous specialists around the world

Seismic Response of the East Flank of the Central Kansas Uplift, Rice County, Kansas

A 7-mi (11.2-km) seismic line across the Lyons anticline just south of Lyons, Rice County, Kansas, shows reflections to the depth of about 3,500 ft (1,070 m) corresponding to the Precambrian Rice Formation. The Lyons anticline is used as a gas storage facility. Although data quality of reflections from the Precambrian is poor, the indication is that the Lyons anticline existed during the Late Proterozoic and that its initial uplift may be related to Keweenawan rifting. Cambrian-Ordovician Arbuckle Group reflections diverge away from the anticline, suggesting that deposition was contemporaneous with uplift. The Middle Ordovician Simpson Group and the Devonian-Mississippian Chattanooga Shale have distinctive reflection characters. Middle and Upper Ordovician Viola and Maquoketa Formations share a single response of a strong transitional, stretched, and positive-polarity peak. Within the Chattanooga Shale is a thin limestone member which forms a distinct positive-polarity reflection. The limestone is seen to truncate over the crest of the Lyons anticline, and apparently thins eastward and is eventually replaced with siltstone. In the Pennsylvanian, the Kansas City, Lansing, and Douglas Groups show a reflection aspect characteristic of a deposition system that is predominantly nonmarine clastic with an associated marginal-marine transport process. Reflections in the Shawnee Group have distinctive but modes amplitude and good continuity. Existence of a possible channel is apparent in the seismic response of the Kanwaka Shale. This feature would be rare to encounter and difficult to characterize if known only from drill data. In the Wabaunsee Group, the Howard Limestone forms a very prominent reflection. The Lower Permian Admire, Council Grove, and Chase Groups have high-amplitude continuous reflections similar to the Wabaunsee, indicating lateral consistency across the section

Seismic Response of the East Flank of the Central Kansas Uplift, Rice County, Kansas

A 7-mi (11.2-km) seismic line across the Lyons anticline just south of Lyons, Rice County, Kansas, shows reflections to the depth of about 3,500 ft (1,070 m) corresponding to the Precambrian Rice Formation. The Lyons anticline is used as a gas storage facility. Although data quality of reflections from the Precambrian is poor, the indication is that the Lyons anticline existed during the Late Proterozoic and that its initial uplift may be related to Keweenawan rifting. Cambrian-Ordovician Arbuckle Group reflections diverge away from the anticline, suggesting that deposition was contemporaneous with uplift. The Middle Ordovician Simpson Group and the Devonian-Mississippian Chattanooga Shale have distinctive reflection characters. Middle and Upper Ordovician Viola and Maquoketa Formations share a single response of a strong transitional, stretched, and positive-polarity peak. Within the Chattanooga Shale is a thin limestone member which forms a distinct positive-polarity reflection. The limestone is seen to truncate over the crest of the Lyons anticline, and apparently thins eastward and is eventually replaced with siltstone. In the Pennsylvanian, the Kansas City, Lansing, and Douglas Groups show a reflection aspect characteristic of a deposition system that is predominantly nonmarine clastic with an associated marginal-marine transport process. Reflections in the Shawnee Group have distinctive but modes amplitude and good continuity. Existence of a possible channel is apparent in the seismic response of the Kanwaka Shale. This feature would be rare to encounter and difficult to characterize if known only from drill data. In the Wabaunsee Group, the Howard Limestone forms a very prominent reflection. The Lower Permian Admire, Council Grove, and Chase Groups have high-amplitude continuous reflections similar to the Wabaunsee, indicating lateral consistency across the section