Germline ETV6 Mutations Confer Susceptibility to Acute Lymphoblastic Leukemia and Thrombocytopenia.
PLoS Genet
; 11(6): e1005262, 2015 Jun.
Article
en 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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Represoras
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Trombocitopenia
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Mutación de Línea Germinal
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Mutación Missense
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Proteínas Proto-Oncogénicas c-ets
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Leucemia-Linfoma Linfoblástico de Células Precursoras
Tipo de estudio:
Observational_studies
/
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
PLoS Genet
Asunto de la revista:
GENETICA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos