DLK1-DIO3 imprinted locus deregulation in development, respiratory disease, and cancer

ABSTRACT

Introduction: The imprinted DLK1-DIO3 locus at 14q32.1–32.31 holds biological significance in fetal development, whereby imprinting errors are causal to developmental disorders. Emerging evidence has implicated this locus in other diseases including cancer, highlighting the biological parallels between fetal organ and tumour development.

Areas covered: Controlled regulation of gene expression from the imprinted DLK1-DIO3 locus at 14q32.1–32.31 is crucial for proper fetal development. Deregulation of locus gene expression due to imprinting errors has been mechanistically linked to the developmental disorders Kagami-Ogata Syndrome and Temple Syndrome. In adult tissues, deregulation of locus genes has been associated with multiple malignancies although the causal genetic mechanisms remain largely uncharacterised. Here, we summarize the genetic mechanisms underlying the developmental disorders that arise as a result of improper locus imprinting and the resulting developmental phenotypes, emphasizing both the coding and noncoding components of the locus. We further highlight biological parallels common to both fetal development and disease, with a specific focus on lung development, respiratory disease, and lung cancer.

Expert commentary: Many commonalities between respiratory and developmental defects have emerged with respect to the 14q32 locus, emphasizing the importance of studying the effects of imprinting on gene regulation patterns at this locus in both biological settings.

KEYWORDS:

• DLK1-DIO3 locus
• imprinting
• uniparental disomy
• fetal development
• developmental disorders
• Temple syndrome
• Kagami-Ogata syndrome
• respiratory disease
• noncoding RNA
• cancer

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This work was supported by a grant from the Canadian Institutes of Health Research (FDN-143345) as well as Frederick Banting and Charles Best Canada Graduate scholarships and scholarships from the University of British Columbia.