Difference between pages "A new malaria agent in African chimpanzees found" and "Recurring Mutations Found by Full length Sequencing of an Acute Myeloid Leukemia Genome (AML)"

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<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="LINE-HEIGHT: 14px; FONT-FAMILY: Verdana; FONT-SIZE: 12px" class="Apple-style-span"><br />
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<strong><font size="4">Recurring Mutations Found by Sequencing an Acute Myeloid Leukemia Genome.&nbsp;<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-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="#0066cc">PLoS Pathog.</font></a></span><span class="Apple-converted-space">&nbsp;</span>2009 May;5(5):e1000446. Epub 2009 May 29<br />
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</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">
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Mardis ER, Ding L, Dooling DJ, Larson DE, McLellan MD, Chen K, 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, Du F, Dukes AF, Sanderson GE, Brummett AM, Clark E, McMichael JF, Meyer RJ, Schindler JK, Pohl CS, Wallis JW, Shi X, Lin L, Schmidt H, Tang Y, Haipek C, 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, Walter MJ, Graubert TA, Dipersio JF, Wilson RK, Ley TJ.&nbsp;<br />
<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></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=%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>,<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 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 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 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>,<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>,<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 Emergentes, Centre International de Recherches M&eacute;dicales de Franceville, Franceville, Gabon.</p>
 
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Researchers&nbsp;reported the discovery of a new Plasmodium species infecting Hominids.&nbsp;<br />
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From 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.); the Genome 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.); and the Division of Biostatistics (J.B.) - all at Washington University, St. Louis. This article (10.1056/NEJMoa0903840) was published on August 5, 2009, at NEJM.org. <br />
New species has been isolated in two chimpanzees (Pan troglodytes) kept as pets by villagers in Gabon (Africa).&nbsp;<br />
 
 
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Analysis of its complete mitochondrial genome (5529 nucleotides including Cyt b, Cox I and Cox III genes) reveals an older divergence of this lineage from the clade that includes [[P. falciparum]] and [[P. reichenowi]] (approximately 21+/-9 Myrs ago using Bayesian methods and considering that the divergence between P. falciparum and P. reichenowi occurred 4 to 7 million years ago as generally considered in the literature).&nbsp;<br />
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<strong>BACKGROUND</strong>: The full complement of DNA mutations that are responsible for the pathogenesis of acute myeloid leukemia (AML) is not yet known.&nbsp;<br />
This time frame would be congruent with the radiation of hominoids, suggesting that this Plasmodium lineage might have been present in early hominoids and that they may both have experienced a simultaneous diversification.<br />
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<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 (AML-M1) and a matched normal skin genome.&nbsp;<br />
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<strong>RESULTS</strong>: We identified 12 acquired (somatic) mutations within the coding sequences of genes and 52 somatic point mutations in conserved or regulatory portions of the genome.&nbsp;<br />
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All mutations appeared to be heterozygous and present in nearly all cells in the tumor sample.&nbsp;<br />
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Four of the 64 mutations occurred in at least 1 additional AML sample in 188 samples that were tested.&nbsp;<br />
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Mutations in NRAS and NPM1 had been identified previously in patients with AML, but two other mutations had not been identified. One of these mutations, in the IDH1 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 />
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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 />
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The AML genome that we sequenced contains approximately 750 point mutations, of which only a small fraction are likely to be relevant to pathogenesis.&nbsp;<br />
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<strong>CONCLUSIONS</strong>: By comparing the sequences of tumor and skin genomes of a patient with AML-M1, we have identified recurring mutations that may be relevant for pathogenesis.&nbsp;<br />
 
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<a href="http://www.ncbi.nlm.nih.gov/pubmed/19478877?ordinalpos=1&amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum"><font color="#0066cc">http://www.ncbi.nlm.nih.gov/pubmed/19478877?ordinalpos=1&amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum</font></a><br />
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<strong>69.9 billion base pairs were sequenced (23.3<font face="arial,helvetica">x</font> haploid coverage)</strong><br />
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Copyright 2009 Massachusetts Medical Society.&nbsp;<br />
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<a href="http://content.nejm.org/cgi/content/full/NEJMoa0903840">http://content.nejm.org/cgi/content/full/NEJMoa0903840</a><br />
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<a href="http://content.nejm.org/cgi/reprint/NEJMoa0903840v1.pdf">http://content.nejm.org/cgi/reprint/NEJMoa0903840v1.pdf</a><br />
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<a href="http://www.ncbi.nlm.nih.gov/pubmed/19657110?ordinalpos=1&amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum">http://www.ncbi.nlm.nih.gov/pubmed/19657110?ordinalpos=1&amp;itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum</a>

Revision as of 01:55, 11 August 2009

Recurring Mutations Found by Sequencing an Acute Myeloid Leukemia Genome. 

Mardis ER, Ding L, Dooling DJ, Larson DE, McLellan MD, Chen K, 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, Du F, Dukes AF, Sanderson GE, Brummett AM, Clark E, McMichael JF, Meyer RJ, Schindler JK, Pohl CS, Wallis JW, Shi X, Lin L, Schmidt H, Tang Y, Haipek C, 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, Walter MJ, Graubert TA, Dipersio JF, Wilson RK, Ley TJ. 

From 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.); the Genome 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.); and the Division of Biostatistics (J.B.) - all at Washington University, St. Louis. This article (10.1056/NEJMoa0903840) was published on August 5, 2009, at NEJM.org.

BACKGROUND: The full complement of DNA mutations that are responsible for the pathogenesis of acute myeloid leukemia (AML) is not yet known. 
METHODS: 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 (AML-M1) and a matched normal skin genome. 
RESULTS: We identified 12 acquired (somatic) mutations within the coding sequences of genes and 52 somatic point mutations in conserved or regulatory portions of the genome. 
All mutations appeared to be heterozygous and present in nearly all cells in the tumor sample. 
Four of the 64 mutations occurred in at least 1 additional AML sample in 188 samples that were tested. 
Mutations in NRAS and NPM1 had been identified previously in patients with AML, but two other mutations had not been identified. One of these mutations, in the IDH1 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%). 
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. 
The AML genome that we sequenced contains approximately 750 point mutations, of which only a small fraction are likely to be relevant to pathogenesis. 
CONCLUSIONS: By comparing the sequences of tumor and skin genomes of a patient with AML-M1, we have identified recurring mutations that may be relevant for pathogenesis. 

69.9 billion base pairs were sequenced (23.3x haploid coverage)

Copyright 2009 Massachusetts Medical Society. 

http://content.nejm.org/cgi/content/full/NEJMoa0903840

http://content.nejm.org/cgi/reprint/NEJMoa0903840v1.pdf

http://www.ncbi.nlm.nih.gov/pubmed/19657110?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum