Secondary MYC translocations in myeloma have been shown to be important in the pathogenesis and progression of disease. Here, we have used a DNA capture and massively parallel sequencing approach to identify the partner chromosomes in 104 presentation myeloma samples. 8q24 breakpoints were identified in 21 (20%) samples with partner loci including IGH, IGK and IGL, which juxtapose the immunoglobulin (Ig) enhancers next to MYC in 8/23 samples. The remaining samples had partner loci including XBP1, FAM46C, CCND1 and KRAS, which are important in B-cell maturation or myeloma pathogenesis. Analysis of the region surrounding the breakpoints indicated the presence of superenhancers on the partner chromosomes and gene expression analysis showed increased expression of MYC in these samples. Patients with MYC translocations had a decreased progression-free and overall survival. We postulate that translocation breakpoints near MYC result in colocalization of the gene with superenhancers from loci, which are important in the development of the cell type in which they occur. In the case of myeloma these are the Ig loci and those important for plasma cell development and myeloma pathogenesis, resulting in increased expression of MYC and an aggressive disease phenotype.

Translocations at 8q24 juxtapose MYC with genes that harbor superenhancers resulting in overexpression and poor prognosis in myeloma patients / Walker BA;Wardell CP;Brioli A;Boyle E;Kaiser MF;Begum DB;Dahir NB;Johnson DC;Ross FM;Davies FE;Morgan GJ. - In: BLOOD CANCER JOURNAL. - ISSN 2044-5385. - ELETTRONICO. - 4:(2014), pp. e191-e191. [10.1038/bcj.2014.13]

Translocations at 8q24 juxtapose MYC with genes that harbor superenhancers resulting in overexpression and poor prognosis in myeloma patients.

BRIOLI, ANNAMARIA;
2014

Abstract

Secondary MYC translocations in myeloma have been shown to be important in the pathogenesis and progression of disease. Here, we have used a DNA capture and massively parallel sequencing approach to identify the partner chromosomes in 104 presentation myeloma samples. 8q24 breakpoints were identified in 21 (20%) samples with partner loci including IGH, IGK and IGL, which juxtapose the immunoglobulin (Ig) enhancers next to MYC in 8/23 samples. The remaining samples had partner loci including XBP1, FAM46C, CCND1 and KRAS, which are important in B-cell maturation or myeloma pathogenesis. Analysis of the region surrounding the breakpoints indicated the presence of superenhancers on the partner chromosomes and gene expression analysis showed increased expression of MYC in these samples. Patients with MYC translocations had a decreased progression-free and overall survival. We postulate that translocation breakpoints near MYC result in colocalization of the gene with superenhancers from loci, which are important in the development of the cell type in which they occur. In the case of myeloma these are the Ig loci and those important for plasma cell development and myeloma pathogenesis, resulting in increased expression of MYC and an aggressive disease phenotype.
2014
Translocations at 8q24 juxtapose MYC with genes that harbor superenhancers resulting in overexpression and poor prognosis in myeloma patients / Walker BA;Wardell CP;Brioli A;Boyle E;Kaiser MF;Begum DB;Dahir NB;Johnson DC;Ross FM;Davies FE;Morgan GJ. - In: BLOOD CANCER JOURNAL. - ISSN 2044-5385. - ELETTRONICO. - 4:(2014), pp. e191-e191. [10.1038/bcj.2014.13]
Walker BA;Wardell CP;Brioli A;Boyle E;Kaiser MF;Begum DB;Dahir NB;Johnson DC;Ross FM;Davies FE;Morgan GJ
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/396680
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