The genetic basis of early T-cell precursor acute lymphoblastic leukaemia
Jinghui Zhang,Li Ding,Linda Holmfeldt,Gang Wu,Susan L. Heatley,Susan L. Heatley,Debbie Payne-Turner,John Easton,Xiang Chen,Jianmin Wang,Michael Rusch,Charles Lu,Shann Ching Chen,Lei Wei,J. Racquel Collins-Underwood,Jing Ma,Kathryn G. Roberts,Stanley Pounds,Anatoly Ulyanov,Jared Becksfort,Pankaj Gupta,Robert Huether,Richard W. Kriwacki,Matthew Parker,Daniel J. McGoldrick,David Zhao,Daniel Alford,Stephen Espy,Kiran Chand Bobba,Guangchun Song,Deqing Pei,Cheng Cheng,Stefan Roberts,Michael I. Barbato,Michael I. Barbato,Dario Campana,Dario Campana,Elaine Coustan-Smith,Elaine Coustan-Smith,Sheila A. Shurtleff,Susana C. Raimondi,Maria Kleppe,Maria Kleppe,Jan Cools,Kristin A. Shimano,Michelle L. Hermiston,Sergei Doulatov,Kolja Eppert,Elisa Laurenti,Faiyaz Notta,John E. Dick,Giuseppe Basso,Stephen P. Hunger,Mignon L. Loh,Meenakshi Devidas,Brent L. Wood,Stuart S. Winter,Kimberley P. Dunsmore,Robert S. Fulton,Lucinda Fulton,Xin Hong,Chris Harris,David J. Dooling,Kerri Ochoa,Kimberly J. Johnson,John C. Obenauer,William E. Evans,Ching-Hon Pui,Clayton W. Naeve,Timothy J. Ley,Elaine R. Mardis,Richard K. Wilson,James R. Downing,Charles G. Mullighan +73 more
TLDR
The mutational spectrum is similar to myeloid tumours, and moreover, the global transcriptional profile of ETP ALL was similar to that of normal andMyeloid leukaemia haematopoietic stem cells, suggesting that addition of myeloids-directed therapies might improve the poor outcome of E TP ALL.Abstract:
Early T-cell precursor acute lymphoblastic leukaemia (ETP ALL) is an aggressive malignancy of unknown genetic basis. We performed whole-genome sequencing of 12 ETP ALL cases and assessed the frequency of the identified somatic mutations in 94 T-cell acute lymphoblastic leukaemia cases. ETP ALL was characterized by activating mutations in genes regulating cytokine receptor and RAS signalling (67% of cases; NRAS, KRAS, FLT3, IL7R, JAK3, JAK1, SH2B3 and BRAF), inactivating lesions disrupting haematopoietic development (58%; GATA3, ETV6, RUNX1, IKZF1 and EP300) and histone-modifying genes (48%; EZH2, EED, SUZ12, SETD2 and EP300). We also identified new targets of recurrent mutation including DNM2, ECT2L and RELN. The mutational spectrum is similar to myeloid tumours, and moreover, the global transcriptional profile of ETP ALL was similar to that of normal and myeloid leukaemia haematopoietic stem cells. These findings suggest that addition of myeloid-directed therapies might improve the poor outcome of ETP ALL.read more
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Signatures of mutational processes in human cancer
Ludmil B. Alexandrov,Serena Nik-Zainal,Serena Nik-Zainal,David C. Wedge,Samuel Aparicio,Sam Behjati,Sam Behjati,Andrew V. Biankin,Graham R. Bignell,Niccolo Bolli,Niccolo Bolli,Åke Borg,Anne Lise Børresen-Dale,Anne Lise Børresen-Dale,Sandrine Boyault,Birgit Burkhardt,Adam Butler,Carlos Caldas,Helen Davies,Christine Desmedt,Roland Eils,Jorunn E. Eyfjord,John A. Foekens,Mel Greaves,Fumie Hosoda,Barbara Hutter,Tomislav Ilicic,Sandrine Imbeaud,Sandrine Imbeaud,Marcin Imielinsk,Natalie Jäger,David T. W. Jones,David T. Jones,Stian Knappskog,Stian Knappskog,Marcel Kool,Sunil R. Lakhani,Carlos López-Otín,Sancha Martin,Nikhil C. Munshi,Nikhil C. Munshi,Hiromi Nakamura,Paul A. Northcott,Marina Pajic,Elli Papaemmanuil,Angelo Paradiso,John V. Pearson,Xose S. Puente,Keiran Raine,Manasa Ramakrishna,Andrea L. Richardson,Andrea L. Richardson,Julia Richter,Philip Rosenstiel,Matthias Schlesner,Ton N. Schumacher,Paul N. Span,Jon W. Teague,Yasushi Totoki,Andrew Tutt,Rafael Valdés-Mas,Marit M. van Buuren,Laura van ’t Veer,Anne Vincent-Salomon,Nicola Waddell,Lucy R. Yates,Icgc PedBrain,Jessica Zucman-Rossi,Jessica Zucman-Rossi,P. Andrew Futreal,Ultan McDermott,Peter Lichter,Matthew Meyerson,Matthew Meyerson,Sean M. Grimmond,Reiner Siebert,Elias Campo,Tatsuhiro Shibata,Stefan M. Pfister,Stefan M. Pfister,Peter J. Campbell,Peter J. Campbell,Peter J. Campbell,Michael R. Stratton,Michael R. Stratton +84 more
TL;DR: It is shown that hypermutation localized to small genomic regions, ‘kataegis’, is found in many cancer types, and this results reveal the diversity of mutational processes underlying the development of cancer.
Journal ArticleDOI
The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia
Daniel A. Arber,Attilio Orazi,Robert P. Hasserjian,Jürgen Thiele,Michael J. Borowitz,Michelle M. Le Beau,Clara D. Bloomfield,Mario Cazzola,James W. Vardiman +8 more
TL;DR: The 2016 edition of the World Health Organization classification of tumors of the hematopoietic and lymphoid tissues represents a revision of the prior classification rather than an entirely new classification and attempts to incorporate new clinical, prognostic, morphologic, immunophenotypic, and genetic data that have emerged since the last edition.
Journal ArticleDOI
Cancer epigenetics: from mechanism to therapy.
Mark A. Dawson,Tony Kouzarides +1 more
TL;DR: The basic principles behind DNA methylation, histone modification, nucleosome remodeling, and RNA-mediated targeting are presented and the evidence suggesting that their misregulation can culminate in cancer is highlighted.
Journal ArticleDOI
Age-related mutations associated with clonal hematopoietic expansion and malignancies
Mingchao Xie,Charles Lu,Jiayin Wang,Michael D. McLellan,Kimberly J. Johnson,Michael C. Wendl,Joshua F. McMichael,Heather Schmidt,Venkata Yellapantula,Christopher A. Miller,Bradley A. Ozenberger,John S. Welch,Daniel C. Link,Matthew J. Walter,Elaine R. Mardis,John F. DiPersio,Feng Chen,Richard K. Wilson,Timothy J. Ley,Li Ding +19 more
TL;DR: The analyses show that the blood cells of more than 2% of individuals contain mutations that may represent premalignant events that cause clonal hematopoietic expansion, and several recurrently mutated genes that may be disease initiators are identified.
Journal ArticleDOI
Acute Lymphoblastic Leukemia in Children
TL;DR: The most common cancer in childhood is now curable in 90% of patients and the subsets of acute lymphoblastic leukemia that are most resistant to current therapy are being targeted.
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