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PHF6 mutations in T-cell acute lymphoblastic leukemia

AuthorsVlierberghe, Pieter van; Palomero, Teresa; Khiabanian, Hossein; Meulen, Joni van der; Castillo, Mireia; Roy, Nadine van; Moerloose, Bárbara de; Philippé, Jan; González-García, Sara ; Toribio, María Luisa ; Taghon, Tom; Zuurbier, Linda; Cauwelier, Bárbara; Harrison, Christine J.; Schwab, Claire; Pisecker, Markus; Strehl, Sabine; Langerak, Anton W.; Gecz, Jozef; Sonneveld, Edwin; Pieters, Rob; Paietta, Elisabeth; Rowe, Jacob M.; Wiernik, Peter H.; Benoit, Yves; Soulier, Jean; Poppe, Bruce; Yao, Xiaopan; Cordón-Cardo, Carlos; Meijerink, Jules; Rabadán, Raúl; Speleman, Frank; Ferrando, Adolfo
KeywordsPHF6 mutations
Lymphoblastic leukemia
Issue Date14-Mar-2010
PublisherNature Publishing Group
CitationNature Genetics
AbstractTumor suppressor genes on the X chromosome may skew the gender distribution of specific types of cancer1, 2. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with an increased incidence in males3. 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.
Publisher version (URL)http://dx.doi.org/10.1038/ng.542
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