The genomic landscape of juvenile myelomonocytic leukemia

被引：216

作者：

Stieglitz, Elliot ^{[1
]}

Taylor-Weiner, Amaro N. ^{[2
]}

Chang, Tiffany Y. ^{[1
]}

Gelston, Laura C. ^{[1
]}

Wang, Yong-Dong ^{[3
]}

Mazor, Tali ^{[4
]}

Esquivel, Emilio ^{[1
]}

Yu, Ariel ^{[1
]}

Seepo, Sara ^{[2
]}

Olsen, Scott R. ^{[5
]}

Rosenberg, Mara ^{[2
]}

Archambeault, Sophie L. ^{[1
]}

Abusin, Ghada ^{[6
]}

Beckman, Kyle ^{[1
]}

Brown, Patrick A. ^{[7
]}

Briones, Michael ^{[8
]}

Carcamo, Benjamin ^{[9
]}

Cooper, Todd ^{[10
]}

Dahl, Gary V. ^{[11
]}

Emanuel, Peter D. ^{[12
]}

Fluchel, Mark N. ^{[13
]}

Goyal, Rakesh K. ^{[14
]}

Hayashi, Robert J. ^{[15
]}

Hitzler, Johann ^{[16
]}

Hugge, Christopher ^{[17
]}

Liu, Y. Lucy

Messinger, Yoav H. ^{[18
]}

Mahoney, Donald H., Jr. ^{[19
]}

Monteleone, Philip ^{[20
]}

Nemecek, Eneida R. ^{[21
]}

Roehrs, Philip A. ^{[22
]}

Schore, Reuven J. ^{[23
]}

Stine, Kimo C. ^{[24
]}

Takemoto, Clifford M. ^{[7
]}

Toretsky, Jeffrey A. ^{[25
,26
]}

Costello, Joseph F.

Olshen, Adam B. ^{[27
,28
]}

Stewart, Chip ^{[2
]}

Li, Yongjin ^{[3
]}

Ma, Jing ^{[29
]}

Gerbing, Robert B. ^{[30
]}

Alonzo, Todd A. ^{[31
]}

Getz, Gad ^{[2
,32
,33
,34
]}

Gruber, Tanja A. ^{[29
,35
]}

Golub, Todd R. ^{[2
,32
,36
,37
]}

Stegmaier, Kimberly ^{[2
,32
,36
,37
]}

Loh, Mignon L. ^{[1
,38
]}

机构：

[1] Univ Calif San Francisco, Dept Pediat, Benioff Childrens Hosp, San Francisco, CA 94143 USA

[2] Broad Inst MIT & Harvard, Cambridge, MA USA

[3] St Jude Childrens Res Hosp, Dept Computat Biol, Memphis, TN 38105 USA

[4] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA

[5] St Jude Childrens Res Hosp, Hartwell Ctr Bioinformat & Biotechnol, Memphis, TN 38105 USA

[6] Univ Iowa, Carver Coll Med, Stead Family Dept Pediat, Iowa City, IA USA

[7] Johns Hopkins Univ Hosp, Dept Pediat, Baltimore, MD 21287 USA

[8] Emory Univ, Sch Med, Dept Pediat, Aflac Canc & Blood Disorder Ctr, Atlanta, GA USA

[9] Texas Tech Univ, Dept Pediat, El Paso, TX USA

[10] Seattle Childrens Hosp, Dept Pediat, Seattle, WA USA

[11] Stanford Sch Med, Dept Pediat, Stanford, CA USA

[12] Univ Arkansas Med Sci, Winthrop P Rockefeller Canc Inst, Little Rock, AR 72205 USA

[13] Univ Utah, Dept Pediat Hematol Oncol, Salt Lake City, UT USA

[14] Univ Pittsburgh, Childrens Hosp Pittsburgh, Med Ctr, Dept Pediat, Pittsburgh, PA 15213 USA

[15] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA

[16] Hosp Sick Children, Div Hematol Oncol, Toronto, ON M5G 1X8, Canada

[17] SSM Cardinal Glennon Childrens Med Ctr, Pediat Hematol Oncol, St Louis, MO USA

[18] Childrens Hosp & Clin Minnesota, Div Pediat Hematol Oncol, Minneapolis, MN USA

[19] Texas Childrens Hosp, Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA

[20] Pediat Specialists Lehigh Valley Hosp, Pediat Hematol Oncol, Bethlehem, PA USA

[21] Oregon Hlth & Sci Univ, Pediat Bone Marrow Transplant Program, Portland, OR 97201 USA

[22] Univ N Carolina, Dept Pediat, Chapel Hill, NC USA

[23] Childrens Natl Med Ctr, Div Pediat Oncol, Washington, DC 20010 USA

[24] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA

[25] Georgetown Univ, Dept Pediat, Washington, DC 20057 USA

[26] Georgetown Univ, Dept Oncol, Washington, DC USA

[27] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA

[28] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA

[29] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA

[30] Childrens Oncol Grp, Dept Stat, Monrovia, CA USA

[31] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA

[32] Harvard Univ, Sch Med, Boston, MA USA

[33] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA

[34] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA

[35] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA

[36] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

[37] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA

[38] Univ Calif San Francisco, Dept Pediat, Benioff Childrens Hosp, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA

来源：

NATURE GENETICS | 2015年 / 47卷 / 11期

基金：

美国国家卫生研究院;

关键词：

GATA2; MUTATIONS; NEUROFIBROMATOSIS TYPE-1; MONOMAC SYNDROME; POINT MUTATIONS; POOR-PROGNOSIS; CBL MUTATIONS; NF1; GENE; LNK; EXPRESSION; CHILDREN;

D O I：

10.1038/ng.3400

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Juvenile myelomonocytic leukemia (JMML) is a myeloproliferative neoplasm (MPN) of childhood with a poor prognosis. Mutations in NF1, NRAS, KRAS, PTPN11 or CBL occur in 85% of patients, yet there are currently no risk stratification algorithms capable of predicting which patients will be refractory to conventional treatment and could therefore be candidates for experimental therapies. In addition, few molecular pathways aside from the RAS-MAPK pathway have been identified that could serve as the basis for such novel therapeutic strategies. We therefore sought to genomically characterize serial samples from patients at diagnosis through relapse and transformation to acute myeloid leukemia to expand knowledge of the mutational spectrum in JMML. We identified recurrent mutations in genes involved in signal transduction, splicing, Polycomb repressive complex 2 (PRC2) and transcription. Notably, the number of somatic alterations present at diagnosis appears to be the major determinant of outcome.

引用

页码：1326 / +

页数：10

共 78 条

[1] Spliceosomal gene mutations are frequent events in the diverse mutational spectrum of chronic myelomonocytic leukemia but largely absent in juvenile myelomonocytic leukemia
Abu Kar, Sarah
Jankowska, Anna
Makishima, Hideki
Visconte, Valeria
Jerez, Andres
Sugimoto, Yuka
Muramatsu, Hideki
Traina, Fabiola
Afable, Manuel
Guinta, Kathryn
Tiu, Ramon V.
Przychodzen, Bartlomiej
Sakaguchi, Hirotoshi
Kojima, Seiji
Sekeres, Mikkael A.
List, Alan F.
McDevitt, Michael A.
Maciejewski, Jaroslaw P.
[J]. HAEMATOLOGICA, 2013, 98 (01) : 107 - 113
[2] X-linked thrombocytopenia (XLT) due to WAS mutations: clinical characteristics, long-term outcome, and treatment options
Albert, Michael H.
Bittner, Tanja C.
Nonoyama, Shigeaki
Notarangelo, Lucia Dora
Burns, Siobhan
Imai, Kohsuke
Espanol, Teresa
Fasth, Anders
Pellier, Isabelle
Strauss, Gabriele
Morio, Tomohiro
Gathmann, Benjamin
Noordzij, Jeroen G.
Fillat, Cristina
Hoenig, Manfred
Nathrath, Michaela
Meindl, Alfons
Pagel, Philipp
Wintergerst, Uwe
Fischer, Alain
Thrasher, Adrian J.
Belohradsky, Bernd H.
Ochs, Hans D.
[J]. BLOOD, 2010, 115 (16) : 3231 - 3238
[3] Development of an allele-specific minimal residual disease assay for patients with juvenile myelomonocytic leukemia
Archambeault, Sophie
Flores, Nikki J.
Yoshimi, Ayami
Kratz, Christian P.
Reising, Miriam
Fischer, Alexandra
Noellke, Peter
Locatelli, Franco
Sedlacek, Petr
Flotho, Christian
Zecca, Marco
Emanuel, Peter D.
Castleberry, Robert P.
Niemeyer, Charlotte M.
Bader, Peter
Loh, Mignon L.
[J]. BLOOD, 2008, 111 (03) : 1124 - 1127
[4] Gene Expression-Based Classification As an Independent Predictor of Clinical Outcome in Juvenile Myelomonocytic Leukemia
Bresolin, Silvia
Zecca, Marco
Flotho, Christian
Trentin, Luca
Zangrando, Andrea
Sainati, Laura
Stary, Jan
de Moerloose, Barbara
Hasle, Henrik
Niemeyer, Charlotte M.
Kronnie, Geertruy Te
Locatelli, Franco
Basso, Giuseppe
[J]. JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (11) : 1919 - 1927
[5] HUMAN ONCOGENE OF THE RAS SUPERFAMILY UNMASKED BY EXPRESSION CDNA CLONING
CHAN, AML
MIKI, T
MEYERS, KA
AARONSON, SA
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (16) : 7558 - 7562
[6] Juvenile myelomonocytic leukemia: A report from the 2nd International JMML Symposium
Chan, Rebecca J.
Cooper, Todd
Kratz, Christian P.
Weiss, Brian
Loh, Mignon L.
[J]. LEUKEMIA RESEARCH, 2009, 33 (03) : 355 - 362
[7] Sustained MEK inhibition abrogates myeloproliferative disease in Nf1 mutant mice
Chang, Tiffany
Krisman, Kimberly
Theobald, Emily Harding
Xu, Jin
Akutagawa, Jon
Lauchle, Jennifer O.
Kogan, Scott
Braun, Benjamin S.
Shannon, Kevin
[J]. JOURNAL OF CLINICAL INVESTIGATION, 2013, 123 (01) : 335 - 339
[8] Bedside to bench in juvenile myelomonocytic leukemia: insights into leukemogenesis from a rare pediatric leukemia
Chang, Tiffany Y.
Dvorak, Christopher C.
Loh, Mignon L.
[J]. BLOOD, 2014, 124 (16) : 2487 - 2497
[9] Initial genome sequencing and analysis of multiple myeloma
Chapman, Michael A.
Lawrence, Michael S.
Keats, Jonathan J.
Cibulskis, Kristian
Sougnez, Carrie
Schinzel, Anna C.
Harview, Christina L.
Brunet, Jean-Philippe
Ahmann, Gregory J.
Adli, Mazhar
Anderson, Kenneth C.
Ardlie, Kristin G.
Auclair, Daniel
Baker, Angela
Bergsagel, P. Leif
Bernstein, Bradley E.
Drier, Yotam
Fonseca, Rafael
Gabriel, Stacey B.
Hofmeister, Craig C.
Jagannath, Sundar
Jakubowiak, Andrzej J.
Krishnan, Amrita
Levy, Joan
Liefeld, Ted
Lonial, Sagar
Mahan, Scott
Mfuko, Bunmi
Monti, Stefano
Perkins, Louise M.
Onofrio, Robb
Pugh, Trevor J.
Rajkumar, S. Vincent
Ramos, Alex H.
Siegel, David S.
Sivachenko, Andrey
Stewart, A. Keith
Trudel, Suzanne
Vij, Ravi
Voet, Douglas
Winckler, Wendy
Zimmerman, Todd
Carpten, John
Trent, Jeff
Hahn, William C.
Garraway, Levi A.
Meyerson, Matthew
Lander, Eric S.
Getz, Gad
Golub, Todd R.
[J]. NATURE, 2011, 471 (7339) : 467 - 472
[10] Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples
Cibulskis, Kristian
Lawrence, Michael S.
Carter, Scott L.
Sivachenko, Andrey
Jaffe, David
Sougnez, Carrie
Gabriel, Stacey
Meyerson, Matthew
Lander, Eric S.
Getz, Gad
[J]. NATURE BIOTECHNOLOGY, 2013, 31 (03) : 213 - 219

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