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.
Institute for Cancer Genetics, Columbia University Medical Center, New York, New York, USA.
Pieter
P
Van Vlierberghe
Teresa
T
Palomero
Hossein
H
Khiabanian
Joni
J
Van der Meulen
Mireia
M
Castillo
Nadine
N
Van Roy
Barbara
B
De Moerloose
Jan
J
Philippé
Sara
S
González-García
María L
ML
Toribio
Tom
T
Taghon
Linda
L
Zuurbier
Barbara
B
Cauwelier
Christine J
CJ
Harrison
Claire
C
Schwab
Markus
M
Pisecker
Sabine
S
Strehl
Anton W
AW
Langerak
Jozef
J
Gecz
Edwin
E
Sonneveld
Rob
R
Pieters
Elisabeth
E
Paietta
Jacob M
JM
Rowe
Peter H
PH
Wiernik
Yves
Y
Benoit
Jean
J
Soulier
Bruce
B
Poppe
Xiaopan
X
Yao
Carlos
C
Cordon-Cardo
Jules
J
Meijerink
Raul
R
Rabadan
Frank
F
Speleman
Adolfo
A
Ferrando
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