English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Genome-wide association studies have identified several risk loci for multiple myeloma (MM); however, the mechanisms by which they influence MM are unknown. Here by using genetic association data and functional characterization, we demonstrate that rs4487645 G>T, the most highly associated variant ( P  = 5.30 × 10 −25 ), resides in an enhancer element 47 kb upstream of the transcription start site of c-Myc-interacting  CDCA7L . The G-risk allele, associated with increased  CDCA7L  expression ( P =1.95 × 10 −36 ), increases IRF4 binding and the enhancer interacts with the  CDCA7L  promoter. We show that suppression of  CDCA7L  limits MM proliferation through apoptosis, and increased  CDCA7L  expression is associated with adverse patient survival. These findings implicate IRF4 - mediated  CDCA7L  expression in MM biology and indicate how germline variation might confer susceptibility to MM.

Multiple myeloma risk variant at 7p15.3 creates an IRF4-binding site and interferes with CDCA7L expression