Analysis of the ten-eleven translocation 2 (TET2) gene in familial myeloproliferative neoplasms.
The JAK2(V617F) mutation does not elucidate the phenotypic variability observed in myeloproliferative neoplasm (MPN) families. A putative tumor suppressor gene, TET2, was recently implicated in MPN and myelodysplastic syndromes through the identification of acquired mutations affecting hematopoietic stem cells. The present study analyzed the TET2 gene in 61 MPN cases from 42 families. Fifteen distinct mutations were identified in 12 (20%) JAK2(V617F)-positive or -negative patients. In a patient with 2 TET2 mutations, the analysis of 5 blood samples at different phases of her disease showed the sequential occurrence of JAK2(V617F) and TET2 mutations concomitantly to the disease evolution. Analysis of familial segregation confirmed that TET2 mutations were not inherited but somatically acquired. TET2 mutations were mainly observed (10 of 12) in patients with primary myelofibrosis or patients with polycythemia vera or essential thrombocythemia who secondarily evolved toward myelofibrosis or acute myeloid leukemia.
Saint-Martin
Cécile
C
Department of Genetics, Assistance Publique-Hopitaux de Paris (AP-HP) Groupe Hospitalier Pitié-Salpétrière, Université Pierre et Marie Curie, Paris, France.
Leroy
Gwendoline
G
Delhommeau
François
F
Panelatti
Gérard
G
Dupont
Sabrina
S
James
Chloé
C
Plo
Isabelle
I
Bordessoule
Dominique
D
Chomienne
Christine
C
Delannoy
André
A
Devidas
Alain
A
Gardembas-Pain
Martine
M
Isnard
Françoise
F
Plumelle
Yves
Y
Bernard
Olivier
O
Vainchenker
William
W
Najman
Albert
A
Bellanné-Chantelot
Christine
C
D000328:Adult; D000368:Aged; D019046:Bone Marrow Neoplasms / Q000235:genetics*; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D049308:Dioxygenases; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000235:genetics*
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D049308:Dioxygenases; C541081:TET2 protein, human