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The Origin and Evolution of Mutations in Acute Myeloid Leukemia

John S. Welch,Timothy J. Ley,Daniel C. Link,Christopher A. Miller,David E. Larson,Daniel C. Koboldt,Lukas D. Wartman,Tamara Lamprecht,Fulu Liu,Jun Xia,Cyriac Kandoth,Robert S. Fulton,Michael D. McLellan,David J. Dooling,John W. Wallis,Ken Chen,Christopher Harris,Heather Schmidt,Joelle Kalicki-Veizer,Charles Lu,Qunyuan Zhang,Gang Li,Michelle D. O’Laughlin,Joshua F. McMichael,Kim D. Delehaunty,Lucinda A. Fulton,Vincent Magrini,Sean McGrath,Ryan Demeter,Tammi L. Vickery,Jasreet Hundal,Lisa L. Cook,Gary W. Swift,JP Reed,Patricia A. Alldredge,Todd Wylie,Jason Walker,Mark A. Watson,Sharon E. Heath,William D. Shannon,Nobish Varghese,Rakesh Nagarajan,Jacqueline E. Payton,Jack Baty,Shashikant Kulkarni,Jeffery M. Klco,Michael H. Tomasson,Peter Westervelt,Matthew J. Walter,Timothy A. Graubert,John F. DiPersio,Ding Li,Elaine R. Mardis,Richard K. Wilson

Biology

clone (Java method)

Somatic evolution in cancer

2012

Most mutations in cancer genomes are thought to be acquired after the initiating event, which may cause genomic instability and drive clonal evolution. However, for acute myeloid leukemia (AML), normal karyotypes are common, and genomic instability is unusual. To better understand clonal evolution in AML, we sequenced the genomes of M3-AML samples with a known initiating event (PML-RARA) versus the genomes of normal karyotype M1-AML samples and the exomes of hematopoietic stem/progenitor cells (HSPCs) from healthy people. Collectively, the data suggest that most of the mutations found in AML genomes are actually random events that occurred in HSPCs before they acquired the initiating mutation; the mutational history of that cell is "captured" as the clone expands. In many cases, only one or two additional, cooperating mutations are needed to generate the malignant founding clone. Cells from the founding clone can acquire additional cooperating mutations, yielding subclones that can contribute to disease progression and/or relapse.

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“The Origin and Evolution of Mutations in Acute Myeloid Leukemia” is a paper by John S. Welch Timothy J. Ley Daniel C. Link Christopher A. Miller David E. Larson Daniel C. Koboldt Lukas D. Wartman Tamara Lamprecht Fulu Liu Jun Xia Cyriac Kandoth Robert S. Fulton Michael D. McLellan David J. Dooling John W. Wallis Ken Chen Christopher Harris Heather Schmidt Joelle Kalicki-Veizer Charles Lu Qunyuan Zhang Gang Li Michelle D. O’Laughlin Joshua F. McMichael Kim D. Delehaunty Lucinda A. Fulton Vincent Magrini Sean McGrath Ryan Demeter Tammi L. Vickery Jasreet Hundal Lisa L. Cook Gary W. Swift JP Reed Patricia A. Alldredge Todd Wylie Jason Walker Mark A. Watson Sharon E. Heath William D. Shannon Nobish Varghese Rakesh Nagarajan Jacqueline E. Payton Jack Baty Shashikant Kulkarni Jeffery M. Klco Michael H. Tomasson Peter Westervelt Matthew J. Walter Timothy A. Graubert John F. DiPersio Ding Li Elaine R. Mardis Richard K. Wilson published in 2012. It has an Open Access status of “bronze”. You can read and download a PDF Full Text of this paper here.