Germline ETV6 Mutations Confer Susceptibility to Acute Lymphoblastic Leukemia and Thrombocytopenia.
PLoS Genet
; 11(6): e1005262, 2015 Jun.
Article
in En
| MEDLINE
| ID: mdl-26102509
ABSTRACT
Somatic mutations affecting ETV6 often occur in acute lymphoblastic leukemia (ALL), the most common childhood malignancy. The genetic factors that predispose to ALL remain poorly understood. Here we identify a novel germline ETV6 p. L349P mutation in a kindred affected by thrombocytopenia and ALL. A second ETV6 p. N385fs mutation was identified in an unrelated kindred characterized by thrombocytopenia, ALL and secondary myelodysplasia/acute myeloid leukemia. Leukemic cells from the proband in the second kindred showed deletion of wild type ETV6 with retention of the ETV6 p. N385fs. Enforced expression of the ETV6 mutants revealed normal transcript and protein levels, but impaired nuclear localization. Accordingly, these mutants exhibited significantly reduced ability to regulate the transcription of ETV6 target genes. Our findings highlight a novel role for ETV6 in leukemia predisposition.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Repressor Proteins
/
Thrombocytopenia
/
Germ-Line Mutation
/
Mutation, Missense
/
Proto-Oncogene Proteins c-ets
/
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Type of study:
Observational_studies
/
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
PLoS Genet
Journal subject:
GENETICA
Year:
2015
Document type:
Article
Affiliation country:
United States