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Long-read sequencing unveils IGH-DUX4 translocation into the silenced IGH allele in B-cell acute lymphoblastic leukemia

IGH@ proto-oncogene translocation is a common oncogenic event in lymphoid lineage cancers such as B-ALL, lymphoma and multiple myeloma. Here, to investigate the interplay between IGH@ proto-oncogene translocation and IGH allelic exclusion, we perform long-read whole-genome and transcriptome sequenci...

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Detalles Bibliográficos
Autores principales: Tian, Liqing, Shao, Ying, Nance, Stephanie, Dang, Jinjun, Xu, Beisi, Ma, Xiaotu, Li, Yongjin, Ju, Bensheng, Dong, Li, Newman, Scott, Zhou, Xin, Schreiner, Patrick, Tseng, Elizabeth, Hon, Ting, Ashby, Meredith, Li, Chunliang, Easton, John, Gruber, Tanja A., Zhang, Jinghui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594946/
https://www.ncbi.nlm.nih.gov/pubmed/31243274
http://dx.doi.org/10.1038/s41467-019-10637-8
Descripción
Sumario:IGH@ proto-oncogene translocation is a common oncogenic event in lymphoid lineage cancers such as B-ALL, lymphoma and multiple myeloma. Here, to investigate the interplay between IGH@ proto-oncogene translocation and IGH allelic exclusion, we perform long-read whole-genome and transcriptome sequencing along with epigenetic and 3D genome profiling of Nalm6, an IGH-DUX4 positive B-ALL cell line. We detect significant allelic imbalance on the wild-type over the IGH-DUX4 haplotype in expression and epigenetic data, showing IGH-DUX4 translocation occurs on the silenced IGH allele. In vitro, this reduces the oncogenic stress of DUX4 high-level expression. Moreover, patient samples of IGH-DUX4 B-ALL have similar expression profile and IGH breakpoints as Nalm6, suggesting a common mechanism to allow optimal dosage of non-toxic DUX4 expression.