PHF6 mutations in T-cell acute lymphoblastic leukemia

被引：241

作者：

Van Vlierberghe, Pieter ^{[1
,2
,3
]}

Palomero, Teresa ^{[1
,4
]}

Khiabanian, Hossein ^{[5
]}

Van der Meulen, Joni ^{[2
]}

Castillo, Mireia ^{[4
]}

Van Roy, Nadine ^{[2
]}

De Moerloose, Barbara ^{[6
]}

Philippe, Jan ^{[7
]}

Gonzalez-Garcia, Sara ^{[8
]}

Toribio, Maria L. ^{[8
]}

Taghon, Tom ^{[7
]}

Zuurbier, Linda ^{[3
]}

Cauwelier, Barbara ^{[9
]}

Harrison, Christine J. ^{[10
]}

Schwab, Claire ^{[10
]}

Pisecker, Markus ^{[11
]}

Strehl, Sabine ^{[11
]}

Langerak, Anton W. ^{[12
]}

Gecz, Jozef ^{[13
,14
]}

Sonneveld, Edwin ^{[15
]}

Pieters, Rob ^{[3
,15
]}

Paietta, Elisabeth ^{[16
]}

Rowe, Jacob M. ^{[17
,18
]}

Wiernik, Peter H. ^{[16
]}

Benoit, Yves ^{[6
]}

Soulier, Jean ^{[19
]}

Poppe, Bruce ^{[2
]}

Yao, Xiaopan ^{[20
]}

Cordon-Cardo, Carlos ^{[4
]}

Meijerink, Jules ^{[3
]}

Rabadan, Raul ^{[5
]}

Speleman, Frank ^{[2
]}

Ferrando, Adolfo ^{[1
,4
,21
]}

机构：

[1] Columbia Univ, Inst Canc Genet, Med Ctr, New York, NY 10027 USA

[2] Ghent Univ Hosp, Ctr Med Genet, B-9000 Ghent, Belgium

[3] Erasmus MC, Dept Pediat Oncol Hematol, Rotterdam, Netherlands

[4] Columbia Univ, Dept Pathol, Med Ctr, New York, NY USA

[5] Columbia Univ, Ctr Computat Biol & Bioinformat, New York, NY USA

[6] Ghent Univ Hosp, Dept Pediat Hemato Oncol, B-9000 Ghent, Belgium

[7] Ghent Univ Hosp, Dept Clin Chem Immunol & Microbiol, B-9000 Ghent, Belgium

[8] UAM, CSIC, Ctr Biol Mol Severo Ochoa, Madrid, Spain

[9] Hosp St Jan, Dept Hematol, Brugge, Belgium

[10] Newcastle Univ, Leukaemia Res Cytogenet Grp, No Inst Canc Res, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England

[11] St Anna Childrens Hosp, Childrens Canc Res Inst, A-1090 Vienna, Austria

[12] Erasmus MC, Dept Immunol, Rotterdam, Netherlands

[13] Univ Adelaide, Dept Genet & Mol Pathol, Adelaide, SA, Australia

[14] Univ Adelaide, Dept Pediat, Adelaide, SA, Australia

[15] DCOG, The Hague, Netherlands

[16] Montefiore Med Ctr N, Bronx, NY USA

[17] Rambam Med Ctr, Haifa, Israel

[18] Technion Israel Inst Technol, Haifa, Israel

[19] Hop St Louis, APHP, INSERM, Hematol Lab,U944, Paris, France

[20] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA

[21] Columbia Univ, Dept Pediat, Med Ctr, New York, NY 10027 USA

来源：

NATURE GENETICS | 2010年 / 42卷 / 04期

基金：

美国国家卫生研究院;

关键词：

FORSSMAN-LEHMANN-SYNDROME; X-INACTIVATION PROFILE; GENE-EXPRESSION; LINKED GENE; CHROMOSOME; PROTEIN;

D O I：

10.1038/ng.542

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Tumor suppressor genes on the X chromosome may skew the gender distribution of specific types of cancer(1,2). T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with an increased incidence in males(3). In this study, we report the identification of inactivating mutations and deletions in the X-linked plant homeodomain finger 6 (PHF6) gene in 16% of pediatric and 38% of adult primary T-ALL samples. Notably, PHF6 mutations are almost exclusively found in T-ALL samples from male subjects. Mutational loss of PHF6 is importantly associated with leukemias driven by aberrant expression of the homeobox transcription factor oncogenes TLX1 and TLX3. Overall, these results identify PHF6 as a new X-linked tumor suppressor in T-ALL and point to a strong genetic interaction between PHF6 loss and aberrant expression of TLX transcription factors in the pathogenesis of this disease.

引用

页码：338 / U95

页数：7

共 28 条

[11] Solution hybrid selection with ultra-long oligonucleotides for massively parallel targeted sequencing [J].

Gnirke, Andreas ;

Melnikov, Alexandre ;

Maguire, Jared ;

Rogov, Peter ;

LeProust, Emily M. ;

Brockman, William ;

Fennell, Timothy ;

Giannoukos, Georgia ;

Fisher, Sheila ;

Russ, Carsten ;

Gabriel, Stacey ;

Jaffe, David B. ;

Lander, Eric S. ;

Nusbaum, Chad .

NATURE BIOTECHNOLOGY, 2009, 27 (02) :182-189

[12] Childhood T-cell acute lymphoblastic leukemia: The Dana-Farber Cancer Institute acute lymphoblastic leukemia consortium experience [J].

Goldberg, JM ;

Silverman, LB ;

Levy, DE ;

Dalton, VK ;

Gelber, RD ;

Lehmann, L ;

Cohen, HJ ;

Sallan, SE ;

Asselin, BL .

JOURNAL OF CLINICAL ONCOLOGY, 2003, 21 (19) :3616-3622

[13] CSL-MAML-dependent Notch1 signaling controls T lineage-specific IL-7Rα gene expression in early human thymopoiesis and leukemia [J].

Gonzalez-Garcia, Sara ;

Garcia-Peydro, Marina ;

Martin-Gayo, Enrique ;

Ballestar, Esteban ;

Esteller, Manel ;

Bornstein, Rafael ;

Luis de la Pompa, Jose ;

Ferrando, Adolfo A. ;

Toribio, Maria L. .

JOURNAL OF EXPERIMENTAL MEDICINE, 2009, 206 (04) :779-791

[14]

KHIABANIAN H, 2010, NATURE PRECEDINGS

[15] Duplication of the MYB oncogene in T cell acute lymphoblastic leukemia [J].

Lahortiga, Idoya ;

De Keersmaecker, Kim ;

Van Vlierberghe, Pieter ;

Graux, Carlos ;

Cauwelier, Barbara ;

Lambert, Frederic ;

Mentens, Nicole ;

Beverloo, H. Berna ;

Pieters, Rob ;

Speleman, Frank ;

Odero, Maria D. ;

Bauters, Marijke ;

Froyen, Guy ;

Marynen, Peter ;

Vandenberghe, Peter ;

Wlodarska, Iwona ;

Meijerink, Jules P. P. ;

Cools, Jan .

NATURE GENETICS, 2007, 39 (05) :593-595

[16] Mutations in PHF6 are associated with Borjeson-Forssman-Lehmann syndrome [J].

Lower, KM ;

Turner, G ;

Kerr, BA ;

Mathews, KD ;

Shaw, MA ;

Gedeon, AK ;

Schelley, S ;

Hoyme, HE ;

White, SM ;

Delatycki, MB ;

Lampe, AK ;

Clayton-Smith, J ;

Stewart, H ;

van Ravenswaay, CMA ;

de Vries, BBA ;

Cox, B ;

Grompe, M ;

Ross, S ;

Thomas, P ;

Mulley, JC ;

Gécz, J .

NATURE GENETICS, 2002, 32 (04) :661-665

[17] DNA repair: The importance of phosphorylating histone H2AX [J].

Lowndes, NF ;

Toh, GWL .

CURRENT BIOLOGY, 2005, 15 (03) :R99-R102

[18] T-cell acute lymphoblastic leukemia in adults: clinical features, immunophenotype, cytogenetics, and outcome from the large randomized prospective trial (UKALL XII/ECOG 2993) [J].

Marks, David I. ;

Paietta, Elisabeth M. ;

Moorman, Anthony V. ;

Richards, Susan M. ;

Buck, Georgina ;

DeWald, Gordon ;

Ferrando, Adolfo ;

Fielding, Adele K. ;

Goldstone, Anthony H. ;

Ketterling, Rhett P. ;

Litzow, Mark R. ;

Luger, Selina M. ;

McMillan, Andrew K. ;

Mansour, Marc R. ;

Rowe, Jacob M. ;

Tallman, Martin S. ;

Lazarus, Hillard M. .

BLOOD, 2009, 114 (25) :5136-5145

[19] ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage [J].

Matsuoka, Shuhei ;

Ballif, Bryan A. ;

Smogorzewska, Agata ;

McDonald, E. Robert, III ;

Hurov, Kristen E. ;

Luo, Ji ;

Bakalarski, Corey E. ;

Zhao, Zhenming ;

Solimini, Nicole ;

Lerenthal, Yaniv ;

Shiloh, Yosef ;

Gygi, Steven P. ;

Elledge, Stephen J. .

SCIENCE, 2007, 316 (5828) :1160-1166

[20] A lentiviral RNAi library for human and mouse genes applied to an arrayed viral high-content screen [J].

Moffat, J ;

Grueneberg, DA ;

Yang, XP ;

Kim, SY ;

Kloepfer, AM ;

Hinkle, G ;

Piqani, B ;

Eisenhaure, TM ;

Luo, B ;

Grenier, JK ;

Carpenter, AE ;

Foo, SY ;

Stewart, SA ;

Stockwell, BR ;

Hacohen, N ;

Hahn, WC ;

Lander, ES ;

Sabatini, DM ;

Root, DE .

CELL, 2006, 124 (06) :1283-1298

← 1 2 3 →