PHF6 mutations in T-cell acute lymphoblastic leukemia.
Tumor suppressor genes on the X chromosome may skew the gender distribution of specific types of cancer. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with an increased incidence in males. 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.
Van Vlierberghe
Pieter
P
Institute for Cancer Genetics, Columbia University Medical Center, New York, New York, USA.
Palomero
Teresa
T
Khiabanian
Hossein
H
Van der Meulen
Joni
J
Castillo
Mireia
M
Van Roy
Nadine
N
De Moerloose
Barbara
B
Philippé
Jan
J
González-García
Sara
S
Toribio
María L
ML
Taghon
Tom
T
Zuurbier
Linda
L
Cauwelier
Barbara
B
Harrison
Christine J
CJ
Schwab
Claire
C
Pisecker
Markus
M
Strehl
Sabine
S
Langerak
Anton W
AW
Gecz
Jozef
J
Sonneveld
Edwin
E
Pieters
Rob
R
Paietta
Elisabeth
E
Rowe
Jacob M
JM
Wiernik
Peter H
PH
Benoit
Yves
Y
Soulier
Jean
J
Poppe
Bruce
B
Yao
Xiaopan
X
Cordon-Cardo
Carlos
C
Meijerink
Jules
J
Rabadan
Raul
R
Speleman
Frank
F
Ferrando
Adolfo
A
D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D041321:Chromosomes, Human, X; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D005260:Female; D016147:Genes, Tumor Suppressor; D008040:Genetic Linkage; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012097:Repressor Proteins
D002352:Carrier Proteins; D018398:Homeodomain Proteins; C502542:PHF6 protein, human; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; C489494:TLX3 protein, human; C071250:TLX1 protein, human