Changes

<span style="WIDOWS: 2; TEXT-TRANSFORM: none; TEXT-INDENT: 0px; BORDER-COLLAPSE: separate; FONT: 16px 'Times New Roman'; WHITE-SPACE: normal; ORPHANS: 2; LETTER-SPACING: normal; COLOR: rgb(0,0,0); WORD-SPACING: 0px; -webkit-border-horizontal-spacing: 0px; -webkit-border-vertical-spacing: 0px; -webkit-text-decorations-in-effect: none; -webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px" class="Apple-style-span"strong><span style="LINE-HEIGHT: 14px; FONT-FAMILY: Verdana; FONT-SIZE: 12px" class="Apple-style-span"><br /><span style="WIDOWS: 2; TEXT-TRANSFORM: none; TEXT-INDENT: 0px; BORDER-COLLAPSE: separate; FONT: 16px 'Times New Roman'; WHITE-SPACE: normal; ORPHANS: 2; LETTER-SPACING: normal; COLOR: rgb(0,0,0); WORD-SPACING: 0px; -webkit-border-horizontal-spacing: 0px; -webkit-border-vertical-spacing: 0px; -webkit-text-decorations-in-effect: none; -webkit-text-font size-adjust: auto; -webkit-text-stroke-width: 0px" class="Apple-style-span"><span style="TEXT-ALIGN: right; FONT-FAMILY: Verdana; FONT-SIZE: 12px" class="Apple-style-span"><span style="VERTICAL-ALIGN: top" title="PLoS pathogens."><a style="VERTICAL-ALIGN: top" href="javascript:AL_get(this, 'jour', 'PLoS Pathog.');"><font color="#0066cc4">PLoS PathogRecurring Mutations Found by Sequencing an Acute Myeloid Leukemia Genome.</font></a></span><span class="Apple-converted-space">&nbsp;</span>2009 May;5(5):e1000446. Epub 2009 May 29<br /></span></span><span style="WIDOWS: 2; TEXT-TRANSFORM: none; TEXT-INDENT: 0px; BORDER-COLLAPSE: separate; FONT: 16px 'Times New Roman'; WHITE-SPACE: normal; ORPHANS: 2; LETTER-SPACING: normal; COLOR: rgb(0,0,0); WORD-SPACING: 0px; -webkit-border-horizontal-spacing: 0px; -webkit-border-vertical-spacing: 0px; -webkit-text-decorations-in-effect: none; -webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px" class="Apple-style-span"><span style="FONT-FAMILY: Verdana; FONT-SIZE: 14px" class="Apple-style-span"><div style="PADDING-BOTTOM: 0px; MARGIN: 0px 0px 0.5em 0.5em; PADDING-LEFT: 0px; PADDING-RIGHT: 0px; FONT-SIZE: 12px; PADDING-TOP: 0px" class="authors"><a style="FONT-WEIGHT: bold" href="http://genomics.org/sites/entrez?Db=pubmed&amp;Cmd=Search&amp;Term=%22Ollomo%20B%22%5BAuthor%5D&amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus"><strong><font color="#0066cc">Ollomo B</font></strong><br /a>Mardis ER, Ding L, Dooling DJ, Larson DE, McLellan MD, Chen K,<span class="Apple-converted-space">&nbsp;</span><a style="FONT-WEIGHT: bold" href="http://genomics.org/sites/entrez?Db=pubmed&amp;Cmd=Search&amp;Term=%22Durand%20P%22%5BAuthor%5D&amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus"><strong><font color="#0066cc">Durand P</font></strong></a>Koboldt DC, Fulton RS, Delehaunty KD, McGrath SD, Fulton LA, Locke DP, Magrini VJ, Abbott RM, Vickery TL, Reed JS, Robinson JS, Wylie T, Smith SM, Carmichael L, Eldred JM, Harris CC, Walker J, Peck JB,<span class="Apple-converted-space">&nbsp;</span><a style="FONT-WEIGHT: bold" href="http://genomics.org/sites/entrez?Db=pubmed&amp;Cmd=Search&amp;Term=%22Prugnolle%20F%22%5BAuthor%5D&amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus"><strong><font color="#0066cc">Prugnolle Du F</font></strong></a>,<span class="Apple-converted-space">&nbsp;</span><a style="FONT-WEIGHT: bold" href="http://genomics.org/sites/entrez?Db=pubmed&amp;Cmd=Search&amp;Term=%22Douzery%20E%22%5BAuthor%5D&amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus"><strong><font color="#0066cc">Douzery Dukes AF, Sanderson GE, Brummett AM, Clark E</font></strong></a>,<span class="Apple-converted-space">&nbsp;</span><a style="FONT-WEIGHT: bold" href="http://genomics.org/sites/entrez?Db=pubmed&amp;Cmd=Search&amp;Term=%22Arnathau%20C%22%5BAuthor%5D&amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus"><strong><font color="#0066cc">Arnathau McMichael JF, Meyer RJ, Schindler JK, Pohl CS, Wallis JW, Shi X, Lin L, Schmidt H, Tang Y, Haipek C</font></strong></a>,<span class="Apple-converted-space">&nbsp;</span><a style="FONT-WEIGHT: bold" href="http://genomics.org/sites/entrez?Db=pubmed&amp;Cmd=Search&amp;Term=%22Nkoghe%20D%22%5BAuthor%5D&amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus"><strong><font color="#0066cc">Nkoghe D</font></strong></a>Wiechert ME, Ivy JV, Kalicki J, Elliott G, Ries RE, Payton JE, Westervelt P, Tomasson MH, Watson MA, Baty J, Heath S, Shannon WD, Nagarajan R, Link DC,<span class="Apple-converted-space">&nbsp;</span><a style="FONT-WEIGHT: bold" href="http://genomics.org/sites/entrez?Db=pubmed&amp;Cmd=Search&amp;Term=%22Leroy%20E%22%5BAuthor%5D&amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus"><strong><font color="#0066cc">Leroy E</font></strong></a>Walter MJ,<span class="Apple-converted-space">&nbsp;</span><a style="FONT-WEIGHT: bold" href="http://genomics.org/sites/entrez?Db=pubmed&amp;Cmd=Search&amp;Term=%22Renaud%20F%22%5BAuthor%5D&amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_RVAbstractPlus"><strong><font color="#0066cc">Renaud F</font></strong></a>.</div><p style="LINE-HEIGHT: 1.2em; MARGIN: 1em 0px 0.5em 0.5em; FONT-SIZE: 11px; PADDING-TOP: 0px" class="affiliation">Unit&eacute; des Maladies Virales EmergentesGraubert TA, Centre International de Recherches M&eacute;dicales de FrancevilleDipersio JF, FrancevilleWilson RK, GabonLey TJ.</p></span></span>&nbsp;<br />

Researchers&nbspFrom the Departments of Genetics (E.R.M., L.D., V.J.M., R.K.W., T.J.L.), Medicine (R.E.R., P.W., M.H.T., S.H., W.D.S., D.C.L., M.J.W., T.A.G., J.F.D., T.J.L.), and Pathology and Immunology (J.E.P., M.A.W., R.N.);reported the discovery of a new Plasmodium species infecting HominidsGenome Center (E.R.M., L.D., D.J.D., D.E.L., M.D.M., K.C., D.C.K., R.S.F., K.D.D., S.D.M., L.A.F., D.P.L., V.J.M., R.M.A., T.L.V., J.S. Reed, J.S. Robinson, T.W., S.M.S., L.C., J.M.E., C.C.H., J.W., J.B.P., F.D., A.F.D., G.E.S., A.M.B., E.C., J.F.M., R.J.M., J.K.S., C.S.P., J.W.W., X.S., L.L., H.S., Y.T., C.H., M.E.W., J.V.I., J.K., G.E., M.A.W., R.K.W., T.J.L.); Siteman Cancer Center (P.W., M.H.T., M.A.W., S.H., W.D.S., R.N., D.C.L., M.J.W., T.A.G., J.F.D., R.K.W., T.J.L.&nbsp);<br />New species has been isolated in two chimpanzees and the Division of Biostatistics (Pan troglodytesJ.B.) kept as pets by villagers in Gabon - all at Washington University, St. Louis. This article (Africa10.1056/NEJMoa0903840)was published on August 5, 2009, at NEJM.org.&nbsp;<br />

Analysis <strong>BACKGROUND</strong>: The full complement of DNA mutations that are responsible for the pathogenesis of its complete mitochondrial acute myeloid leukemia (AML) is not yet known.&nbsp;<br /><strong>METHODS</strong>: We used massively parallel DNA sequencing to obtain a very high level of coverage (approximately 98%) of a primary, cytogenetically normal, de novo genome for AML with minimal maturation (5529 nucleotides including Cyt b, Cox I AML-M1) and Cox III a matched normal skin genome.&nbsp;<br /><strong>RESULTS</strong>: We identified 12 acquired (somatic) mutations within the coding sequences of genes) reveals an older divergence and 52 somatic point mutations in conserved or regulatory portions of this lineage from the clade that includes [[Pgenome. falciparum]] &nbsp;<br />All mutations appeared to be heterozygous and [[Ppresent in nearly all cells in the tumor sample. reichenowi]] (approximately 21+&nbsp;<br /-9 Myrs ago using Bayesian methods and considering >Four of the 64 mutations occurred in at least 1 additional AML sample in 188 samples that the divergence between Pwere tested. falciparum &nbsp;<br />Mutations in NRAS and PNPM1 had been identified previously in patients with AML, but two other mutations had not been identified. reichenowi occurred 4 to 7 million years ago as generally considered One of these mutations, in the literatureIDH1 gene, was present in 15 of 187 additional AML genomes tested and was strongly associated with normal cytogenetic status; it was present in 13 of 80 cytogenetically normal samples (16%).&nbsp;<br />This time frame would The other was a nongenic mutation in a genomic region with regulatory potential and conservation in higher mammals; we detected it in one additional AML tumor.&nbsp;<br />The AML genome that we sequenced contains approximately 750 point mutations, of which only a small fraction are likely to be congruent with relevant to pathogenesis.&nbsp;<br /><strong>CONCLUSIONS</strong>: By comparing the radiation sequences of hominoidstumor and skin genomes of a patient with AML-M1, suggesting that this Plasmodium lineage might we have been present in early hominoids and identified recurring mutations that they may both have experienced a simultaneous diversificationbe relevant for pathogenesis.&nbsp;<br />

<strong>69.9 billion base pairs were sequenced (23.3<font face="arial,helvetica">x</font> haploid coverage)</strong><br /><br />Copyright 2009 Massachusetts Medical Society.&nbsp;<br /><br /><a href="http://content.nejm.org/cgi/content/full/NEJMoa0903840">http://content.nejm.org/cgi/content/full/NEJMoa0903840</a><br /><br /><a href="http://content.nejm.org/cgi/reprint/NEJMoa0903840v1.pdf">http://content.nejm.org/cgi/reprint/NEJMoa0903840v1.pdf</a><br /><br /><a href="http://www.ncbi.nlm.nih.gov/pubmed/1947887719657110?ordinalpos=1&amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum"><font color="#0066cc">http://www.ncbi.nlm.nih.gov/pubmed/1947887719657110?ordinalpos=1&amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum</font></a><br /></span></span>