Identification of a HMGA2-EFCAB6 gene rearrangement following next-generation sequencing in a patient with a t(12;22)(q14.3;q13.2) and JAK2V617F-positive myeloproliferative neoplasm.
Cancer Genet
; 205(6): 295-303, 2012 Jun.
Article
em En
| MEDLINE
| ID: mdl-22749035
ABSTRACT
Myeloproliferative neoplasms (MPNs) result from genetically altered hematopoietic stem cells that retain the capacity for multilineage differentiation. The study of genomic mutations identified so far suggests that they occur after a common ancestral event or that different mutations result in similar MPN phenotypes. We report analysis of a chromosomal translocation, t(12;22)(q14.3;q13.2), in a patient with a BCR-ABL1-negative, JAK2V617F-positive MPN. Comparative genomic hybridization (CGH) array and targeted sequencing detected no mutation in nine genes reported to influence the JAK2V617F-driven MPNs (MPL, LNK, CBL, TET2, EZH2, IKZF1, IDH1, IDH2, ASXL1). Next-generation sequencing revealed a balanced HMGA2-EFCAB6 genomic rearrangement. The HMGA2 breakpoint leads to the loss of seven 3'UTR binding sites for the microRNA (miRNA) let-7 tumor suppressor. The breakpoint in the EFCAB6 gene abrogates transcription of EFCAB6. Measurement of expression showed retention of HMGA2 transcription and no detectable EFCAB6 transcript. Allele burden comparison in a sample containing the translocation, showed 90% HMGA2-EFCAB6 versus 50% JAK2V617F allele dose, suggesting HMGA2-EFCAB6 rearrangement plays a more ancestral role, pre-JAK2V617F, in the neoplastic process. The pathogenicity of the translocation may rest on collaborations among JAK2V617F-induced constitutive activation of JAK2, the oncogenic property of HMGA2, and disrupted pathways, such as alteration in DJ-1 expression, resulting from the impact of EFCAB6 abrogation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Translocação Genética
/
Proteína HMGA2
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Janus Quinase 2
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Transtornos Mieloproliferativos
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Aged
/
Female
/
Humans
Idioma:
En
Revista:
Cancer Genet
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos