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Induction and Diagnosis of Tumors in Drosophila Imaginal Disc Epithelia
Published on: July 25, 2017
Dicer1 functions as a haploinsufficient tumor suppressor
Madhu S Kumar1, Ryan E Pester, Cindy Y Chen
1Massachusetts Institute of Technology Koch Institute for Integrative Cancer Research, Cambridge, Massachusetts 02139, USA.
Genes & Development
|November 12, 2009
Summary
Dicer1 acts as a tumor suppressor gene, with only one functional copy needed to inhibit cancer. Loss of one Dicer1 copy in tumors reduces survival, indicating its haploinsufficiency in cancer development.
Area of Science:
- Genetics
- Molecular Biology
- Oncology
Background:
- Global microRNA (miRNA) down-regulation is common in human tumors.
- The genetic underpinnings of miRNA dysregulation in cancer remain largely unknown.
Purpose of the Study:
- To investigate the role of Dicer1, a key miRNA processing enzyme, in tumor suppression.
- To determine if Dicer1 functions as a haploinsufficient tumor suppressor gene.
Main Methods:
- Conditional Dicer1 mutation (Dicer1 "floxed" or Dicer1(fl)) was analyzed in mouse cancer models.
- Tumorigenesis and survival rates were compared between Dicer1(fl/+) and control animals.
- Human cancer genome copy number data for DICER1 was analyzed.
Main Results:
- Deletion of one Dicer1 copy in Dicer1(fl/+) tumors impaired miRNA processing and reduced survival.
- Tumors from Dicer1(fl/fl) animals retained at least one functional Dicer1 allele, suggesting selection against complete loss.
- Enforced Dicer1 deletion inhibited tumorigenesis.
- Human cancer data shows frequent DICER1 deletion, but not homozygous deletion, supporting haploinsufficiency.
Conclusions:
- Dicer1 functions as a haploinsufficient tumor suppressor gene.
- DICER1 haploinsufficiency is implicated in human cancer.
- Other miRNA biogenesis factors may also act as haploinsufficient tumor suppressors.
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