Functional analysis of germline ETV6 W380R mutation causing inherited thrombocytopenia and secondary acute lymphoblastic leukemia or essential thrombocythemia
| Autor: | Šárka Pospíšilová, Jiri Baloun, Sona Mejstrikova, Marketa Zaliova Kubricanova, František Folber, Michael Doubek, Lenka Radová, Zuzana Vrzalová, Katerina Stano Kozubik, Michal Šmída, Michaela Pesova, Kamila Réblová |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Genetics Mutation Somatic cell Hematology General Medicine 030204 cardiovascular system & hematology Biology medicine.disease medicine.disease_cause Germline 3. Good health 03 medical and health sciences ETV6 Leukemia Exon 030104 developmental biology 0302 clinical medicine Germline mutation hemic and lymphatic diseases medicine Exome sequencing |
| Zdroj: | Platelets. 32:838-841 |
| ISSN: | 1369-1635 0953-7104 |
| Popis: | Germline mutations in ETV6 gene cause inherited thrombocytopenia with leukemia predisposition. Here, we report on functional validation of ETV6 W380R mutation segregating with thrombocytopenia in a family where two family members also suffered from acute lymphoblastic leukemia (ALL) or essential thrombocythemia (ET). In-silico analysis predicted impaired DNA binding due to W380R mutation. Functional analysis showed that this mutation prevents the ETV6 protein from localizing into the cell nucleus and impairs the transcriptional repression activity of ETV6. Based on the germline ETV6 mutation, ET probably started with somatic JAK2 V617F mutation, whereas ALL could be caused by diverse mechanisms: high-hyperdiploidity; somatic deletion of exon 1 IKZF1 gene; or somatic mutations of other genes found by exome sequencing of the ALL sample taken at the diagnosis. |
| Databáze: | OpenAIRE |
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