BACKGROUND: Genomic analysis is essential for risk stratification in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). Whole-genome sequencing is a potential replacement for conventional cytogenetic and sequencing approaches, but its accuracy, feasibility, and clinical utility have not been demonstrated. METHODS: We used a streamlined whole-genome sequencing approach to obtain genomic profiles for 263 patients with myeloid cancers, including 235 patients who had undergone successful cytogenetic analysis. We adapted sample preparation, sequencing, and analysis to detect mutations for risk stratification using existing European Leukemia Network (ELN) guidelines and to minimize turnaround time. We analyzed the performance of whole-genome sequencing by comparing our results with findings from cytogenetic analysis and targeted sequencing. RESULTS: Whole-genome sequencing detected all 40 recurrent translocations and 91 copy-number alterations that had been identified by cytogenetic analysis. In addition, we identified new clinically reportable genomic events in 40 of 235 patients (17.0%). Prospective sequencing of samples obtained from 117 consecutive patients was performed in a median of 5 days and provided new genetic information in 29 patients (24.8%), which changed the risk category for 19 patients (16.2%). Standard AML risk groups, as defined by sequencing results instead of cytogenetic analysis, correlated with clinical outcomes. Whole-genome sequencing was also used to stratify patients who had inconclusive results by cytogenetic analysis into risk groups in which clinical outcomes were measurably different. CONCLUSIONS: In our study, we found that whole-genome sequencing provided rapid and accurate genomic profiling in patients with AML or MDS. Such sequencing also provided a greater diagnostic yield than conventional cytogenetic analysis and more efficient risk stratification on the basis of standard risk categories. (Funded by the Siteman Cancer Research Fund and others.).
BACKGROUND: Genomic analysis is essential for risk stratification in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). Whole-genome sequencing is a potential replacement for conventional cytogenetic and sequencing approaches, but its accuracy, feasibility, and clinical utility have not been demonstrated. METHODS: We used a streamlined whole-genome sequencing approach to obtain genomic profiles for 263 patients with myeloid cancers, including 235 patients who had undergone successful cytogenetic analysis. We adapted sample preparation, sequencing, and analysis to detect mutations for risk stratification using existing European Leukemia Network (ELN) guidelines and to minimize turnaround time. We analyzed the performance of whole-genome sequencing by comparing our results with findings from cytogenetic analysis and targeted sequencing. RESULTS: Whole-genome sequencing detected all 40 recurrent translocations and 91 copy-number alterations that had been identified by cytogenetic analysis. In addition, we identified new clinically reportable genomic events in 40 of 235 patients (17.0%). Prospective sequencing of samples obtained from 117 consecutive patients was performed in a median of 5 days and provided new genetic information in 29 patients (24.8%), which changed the risk category for 19 patients (16.2%). Standard AML risk groups, as defined by sequencing results instead of cytogenetic analysis, correlated with clinical outcomes. Whole-genome sequencing was also used to stratify patients who had inconclusive results by cytogenetic analysis into risk groups in which clinical outcomes were measurably different. CONCLUSIONS: In our study, we found that whole-genome sequencing provided rapid and accurate genomic profiling in patients with AML or MDS. Such sequencing also provided a greater diagnostic yield than conventional cytogenetic analysis and more efficient risk stratification on the basis of standard risk categories. (Funded by the Siteman Cancer Research Fund and others.).
Authors: Peter L Greenberg; Heinz Tuechler; Julie Schanz; Guillermo Sanz; Guillermo Garcia-Manero; Francesc Solé; John M Bennett; David Bowen; Pierre Fenaux; Francois Dreyfus; Hagop Kantarjian; Andrea Kuendgen; Alessandro Levis; Luca Malcovati; Mario Cazzola; Jaroslav Cermak; Christa Fonatsch; Michelle M Le Beau; Marilyn L Slovak; Otto Krieger; Michael Luebbert; Jaroslaw Maciejewski; Silvia M M Magalhaes; Yasushi Miyazaki; Michael Pfeilstöcker; Mikkael Sekeres; Wolfgang R Sperr; Reinhard Stauder; Sudhir Tauro; Peter Valent; Teresa Vallespi; Arjan A van de Loosdrecht; Ulrich Germing; Detlef Haase Journal: Blood Date: 2012-06-27 Impact factor: 22.113
Authors: Richard F Schlenk; Konstanze Döhner; Jürgen Krauter; Stefan Fröhling; Andrea Corbacioglu; Lars Bullinger; Marianne Habdank; Daniela Späth; Michael Morgan; Axel Benner; Brigitte Schlegelberger; Gerhard Heil; Arnold Ganser; Hartmut Döhner Journal: N Engl J Med Date: 2008-05-01 Impact factor: 91.245
Authors: Daniel A Arber; Attilio Orazi; Robert Hasserjian; Jürgen Thiele; Michael J Borowitz; Michelle M Le Beau; Clara D Bloomfield; Mario Cazzola; James W Vardiman Journal: Blood Date: 2016-04-11 Impact factor: 22.113
Authors: Timothy J Ley; Christopher Miller; Li Ding; Benjamin J Raphael; Andrew J Mungall; A Gordon Robertson; Katherine Hoadley; Timothy J Triche; Peter W Laird; Jack D Baty; Lucinda L Fulton; Robert Fulton; Sharon E Heath; Joelle Kalicki-Veizer; Cyriac Kandoth; Jeffery M Klco; Daniel C Koboldt; Krishna-Latha Kanchi; Shashikant Kulkarni; Tamara L Lamprecht; David E Larson; Ling Lin; Charles Lu; Michael D McLellan; Joshua F McMichael; Jacqueline Payton; Heather Schmidt; David H Spencer; Michael H Tomasson; John W Wallis; Lukas D Wartman; Mark A Watson; John Welch; Michael C Wendl; Adrian Ally; Miruna Balasundaram; Inanc Birol; Yaron Butterfield; Readman Chiu; Andy Chu; Eric Chuah; Hye-Jung Chun; Richard Corbett; Noreen Dhalla; Ranabir Guin; An He; Carrie Hirst; Martin Hirst; Robert A Holt; Steven Jones; Aly Karsan; Darlene Lee; Haiyan I Li; Marco A Marra; Michael Mayo; Richard A Moore; Karen Mungall; Jeremy Parker; Erin Pleasance; Patrick Plettner; Jacquie Schein; Dominik Stoll; Lucas Swanson; Angela Tam; Nina Thiessen; Richard Varhol; Natasja Wye; Yongjun Zhao; Stacey Gabriel; Gad Getz; Carrie Sougnez; Lihua Zou; Mark D M Leiserson; Fabio Vandin; Hsin-Ta Wu; Frederick Applebaum; Stephen B Baylin; Rehan Akbani; Bradley M Broom; Ken Chen; Thomas C Motter; Khanh Nguyen; John N Weinstein; Nianziang Zhang; Martin L Ferguson; Christopher Adams; Aaron Black; Jay Bowen; Julie Gastier-Foster; Thomas Grossman; Tara Lichtenberg; Lisa Wise; Tanja Davidsen; John A Demchok; Kenna R Mills Shaw; Margi Sheth; Heidi J Sofia; Liming Yang; James R Downing; Greg Eley Journal: N Engl J Med Date: 2013-05-01 Impact factor: 91.245
Authors: John S Welch; Allegra A Petti; Christopher A Miller; Catrina C Fronick; Michelle O'Laughlin; Robert S Fulton; Richard K Wilson; Jack D Baty; Eric J Duncavage; Bevan Tandon; Yi-Shan Lee; Lukas D Wartman; Geoffrey L Uy; Armin Ghobadi; Michael H Tomasson; Iskra Pusic; Rizwan Romee; Todd A Fehniger; Keith E Stockerl-Goldstein; Ravi Vij; Stephen T Oh; Camille N Abboud; Amanda F Cashen; Mark A Schroeder; Meagan A Jacoby; Sharon E Heath; Kierstin Luber; Megan R Janke; Andrew Hantel; Niloufer Khan; Madina J Sukhanova; Randall W Knoebel; Wendy Stock; Timothy A Graubert; Matthew J Walter; Peter Westervelt; Daniel C Link; John F DiPersio; Timothy J Ley Journal: N Engl J Med Date: 2016-11-24 Impact factor: 91.245
Authors: Eric J Duncavage; Meagan A Jacoby; Gue Su Chang; Christopher A Miller; Natasha Edwin; Jin Shao; Kevin Elliott; Joshua Robinson; Haley Abel; Robert S Fulton; Catrina C Fronick; Michelle O'Laughlin; Sharon E Heath; Kimberly Brendel; Raya Saba; Lukas D Wartman; Matthew J Christopher; Iskra Pusic; John S Welch; Geoffrey L Uy; Daniel C Link; John F DiPersio; Peter Westervelt; Timothy J Ley; Kathryn Trinkaus; Timothy A Graubert; Matthew J Walter Journal: N Engl J Med Date: 2018-09-13 Impact factor: 91.245
Authors: Michael Rusch; Joy Nakitandwe; Sheila Shurtleff; Scott Newman; Zhaojie Zhang; Michael N Edmonson; Matthew Parker; Yuannian Jiao; Xiaotu Ma; Yanling Liu; Jiali Gu; Michael F Walsh; Jared Becksfort; Andrew Thrasher; Yongjin Li; James McMurry; Erin Hedlund; Aman Patel; John Easton; Donald Yergeau; Bhavin Vadodaria; Ruth G Tatevossian; Susana Raimondi; Dale Hedges; Xiang Chen; Kohei Hagiwara; Rose McGee; Giles W Robinson; Jeffery M Klco; Tanja A Gruber; David W Ellison; James R Downing; Jinghui Zhang Journal: Nat Commun Date: 2018-09-27 Impact factor: 14.919
Authors: Timothy J Ley; Elaine R Mardis; Li Ding; Bob Fulton; Michael D McLellan; Ken Chen; David Dooling; Brian H Dunford-Shore; Sean McGrath; Matthew Hickenbotham; Lisa Cook; Rachel Abbott; David E Larson; Dan C Koboldt; Craig Pohl; Scott Smith; Amy Hawkins; Scott Abbott; Devin Locke; Ladeana W Hillier; Tracie Miner; Lucinda Fulton; Vincent Magrini; Todd Wylie; Jarret Glasscock; Joshua Conyers; Nathan Sander; Xiaoqi Shi; John R Osborne; Patrick Minx; David Gordon; Asif Chinwalla; Yu Zhao; Rhonda E Ries; Jacqueline E Payton; Peter Westervelt; Michael H Tomasson; Mark Watson; Jack Baty; Jennifer Ivanovich; Sharon Heath; William D Shannon; Rakesh Nagarajan; Matthew J Walter; Daniel C Link; Timothy A Graubert; John F DiPersio; Richard K Wilson Journal: Nature Date: 2008-11-06 Impact factor: 49.962
Authors: Ghayas C Issa; Farhad Ravandi; Courtney D DiNardo; Elias Jabbour; Hagop M Kantarjian; Michael Andreeff Journal: Leukemia Date: 2021-06-15 Impact factor: 11.528
Authors: Kornelia Neveling; Tuomo Mantere; Susan Vermeulen; Michiel Oorsprong; Ronald van Beek; Ellen Kater-Baats; Marc Pauper; Guillaume van der Zande; Dominique Smeets; Daniel Olde Weghuis; Marian J P L Stevens-Kroef; Alexander Hoischen Journal: Am J Hum Genet Date: 2021-07-07 Impact factor: 11.025