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  • 1
    Publication Date: 2014-01-07
    Description: Although a few cancer genes are mutated in a high proportion of tumours of a given type (〉20%), most are mutated at intermediate frequencies (2-20%). To explore the feasibility of creating a comprehensive catalogue of cancer genes, we analysed somatic point mutations in exome sequences from 4,742 human cancers and their matched normal-tissue samples across 21 cancer types. We found that large-scale genomic analysis can identify nearly all known cancer genes in these tumour types. Our analysis also identified 33 genes that were not previously known to be significantly mutated in cancer, including genes related to proliferation, apoptosis, genome stability, chromatin regulation, immune evasion, RNA processing and protein homeostasis. Down-sampling analysis indicates that larger sample sizes will reveal many more genes mutated at clinically important frequencies. We estimate that near-saturation may be achieved with 600-5,000 samples per tumour type, depending on background mutation frequency. The results may help to guide the next stage of cancer genomics.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4048962/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4048962/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lawrence, Michael S -- Stojanov, Petar -- Mermel, Craig H -- Robinson, James T -- Garraway, Levi A -- Golub, Todd R -- Meyerson, Matthew -- Gabriel, Stacey B -- Lander, Eric S -- Getz, Gad -- R01 CA157304/CA/NCI NIH HHS/ -- T32 GM007753/GM/NIGMS NIH HHS/ -- U54 HG003067/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jan 23;505(7484):495-501. doi: 10.1038/nature12912. Epub 2014 Jan 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA. ; 1] Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA [2] Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, Massachusetts 02215, USA. ; 1] Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA [2] Massachusetts General Hospital, Cancer Center and Department of Pathology, 55 Fruit Street, Boston, Massachusetts 02114, USA. ; 1] Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA [2] Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, Massachusetts 02215, USA [3] Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA. ; 1] Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA [2] Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, Massachusetts 02215, USA [3] Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA [4] Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, Maryland 20815, USA. ; 1] Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA [2] Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA [3] Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA [4]. ; 1] Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA [2] Massachusetts General Hospital, Cancer Center and Department of Pathology, 55 Fruit Street, Boston, Massachusetts 02114, USA [3] Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA [4].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24390350" target="_blank"〉PubMed〈/a〉
    Keywords: Apoptosis/genetics ; Case-Control Studies ; Cell Proliferation ; Chromatin/genetics ; DNA Mutational Analysis ; Exome/genetics ; Genes, Neoplasm/*genetics ; Genome, Human/genetics ; Genomic Instability/genetics ; Genomics ; Humans ; Immune Evasion/genetics ; Mutation Rate ; Neoplasms/*classification/*genetics/pathology ; Point Mutation/genetics ; RNA Processing, Post-Transcriptional/genetics ; Sample Size
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 186 (1960), S. 456-458 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] DR. L. S. B. LEAKEY recently reported in Nature^ the discovery of an essentially complete hominid skull without mandible from site FLK at Olduvai Gorge. He regards the specimen as an australo-pithecine that differs more from either of the two known genera, Australopithecus and Paranthropus, than ...
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  • 3
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    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 184 (1959), S. 583-585 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] A MEASURE of controversy has been aroused by-Dart's thesis that Australopithecus used bones, horns and teeth as implements. Evidence for this view has mainly come from Makapansgat, but it is the purpose of this article to report the discovery of a bone implement at Sterkfontein. This single find ...
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  • 4
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    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 171 (1953), S. 33-33 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Hitherto the known specimens of this form comprised only the almost complete mandible containing five molars, P3 belonging to the left side of the same mandible and the proximal end of a radius. The teeth are small compared to the P. crassidens homo-logues-especially Mx. The length and breadth ...
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  • 5
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    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 164 (1949), S. 841-842 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] ONE of the most noteworthy differences between man and the higher anthropoids is that while man has a good opposable thumb, in the anthropoid the thumb is somewhat degenerate. It was mainly on this character that Osborn decided that man could not have evolved from an anthropoid. Though we ...
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  • 6
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    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 160 (1947), S. 153-153 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] ON June 24, we blasted out at Sterkfontein, at a spot only about 8 ft. away from where we discovered the old female skull of Plesianthropus, the almost perfect lower jaw of a large male. The left mandible is complete except for the loss of the condyle and a little part of the margin of the ...
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  • 7
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 180 (1957), S. 521-522 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] IN May 1956 Dr. C. K. Brain, at that time working in the Department of Vertebrate Palaeontology and Physical Anthropology of the Transvaal Museum on the australopithecine-bearing breccias, discovered some stone artefacts in breccia rubble near a small pit 55 ft. west of the Sterkfontein Type Site. ...
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  • 8
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    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 174 (1954), S. 1197-1198 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] This evidence is most clearly seen in the Swartkrans skull SKA9, the occipital region of which has now been prepared in acetic acid. The skull has been sheared considerably, but the region from slightly posterior to the glabella to approximately the position of the bregma, as well as a good deal of ...
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  • 9
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    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 174 (1954), S. 262-263 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] IN a recently published essay1, Prof. S. Zuckerman has discussed at some length the evolutionary position of the australopithecines under the three headings of evidence relating to: (1) the brain, (2) the face and teeth, and (3) upright posture. The first two sections are dismissed after very brief ...
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  • 10
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 185 (1960), S. 407-408 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The molar appears to be a somewhat aberrant specimen, since the morphologically less-stable areas anterior and posterior foveae and either the lingual or buccal faces, depending on whether the tooth is maxillary or mandibular have many accessory cusps. Assuming the tooth to be mandibular, as ...
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