Germline deletion of ETV6 in familial acute lymphoblastic leukemia.
Blood Adv
; 3(7): 1039-1046, 2019 04 09.
Article
en En
| MEDLINE
| ID: mdl-30940639
ABSTRACT
Recent studies have identified germline mutations in TP53, PAX5, ETV6, and IKZF1 in kindreds with familial acute lymphoblastic leukemia (ALL), but the genetic basis of ALL in many kindreds is unknown despite mutational analysis of the exome. Here, we report a germline deletion of ETV6 identified by linkage and structural variant analysis of whole-genome sequencing data segregating in a kindred with thrombocytopenia, B-progenitor acute lymphoblastic leukemia, and diffuse large B-cell lymphoma. The 75-nt deletion removed the ETV6 exon 7 splice acceptor, resulting in exon skipping and protein truncation. The ETV6 deletion was also identified by optimal structural variant analysis of exome sequencing data. These findings identify a new mechanism of germline predisposition in ALL and implicate ETV6 germline variation in predisposition to lymphoma. Importantly, these data highlight the importance of germline structural variant analysis in the search for germline variants predisposing to familial leukemia.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Represoras
/
Eliminación de Secuencia
/
Mutación de Línea Germinal
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Proteínas Proto-Oncogénicas c-ets
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Leucemia-Linfoma Linfoblástico de Células Precursoras
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Blood Adv
Año:
2019
Tipo del documento:
Article
País de afiliación:
Túnez