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Updated: Aug 21, 2026
Isolation, Enrichment, and Maintenance of Medulloblastoma Stem Cells
Published on: September 1, 2010
Chromosome 17p deletion in human medulloblastoma: a missing checkpoint in the Hedgehog pathway
Enrico De Smaele1, Lucia Di Marcotullio, Elisabetta Ferretti
1Department of Experimental Medicine and Pathology, University La Sapienza, Rome, Italy.
Abstract:
Although deregulation of Hedgehog signalling is considered to play a crucial oncogenic role and commonly occurrs in medulloblastoma, genetic lesions in components of this pathway are observed in a minority of cases. The recent identification of a novel putative tumor suppressor (REN(KCTD11)) on chromosome 17p13.2, a region most frequently lost in human medulloblastoma, highlights the role of allelic deletion of the gene in this brain malignancy, leading to the loss of growth inhibitory activity via suppression of Gli-dependent activation of Hedgehog target genes. The presence on 17p13 of another tumor suppressor gene (p53) whose inactivation cooperates with Hedgehog pathway for medulloblastoma formation, suggests that 17p deletion unveils haploinsufficiency conditions leading to abrogation of either direct and indirect checkpoints of Hedgehog signalling in cancer.
Insights
Deregulation of Hedgehog signaling contributes to medulloblastoma. Loss of the REN (KCTD11) tumor suppressor gene on chromosome 17p13.2 impairs growth inhibition, promoting brain cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Hedgehog signaling pathway deregulation is implicated in medulloblastoma pathogenesis.
- Genetic alterations in pathway components are found in a subset of medulloblastoma cases.
- Chromosome 17p13.2, frequently lost in medulloblastoma, harbors tumor suppressor genes.
Purpose of the Study:
- To investigate the role of the novel tumor suppressor REN (KCTD11) in medulloblastoma.
- To understand the impact of allelic deletion of REN (KCTD11) on Hedgehog signaling.
- To explore the contribution of 17p deletions to medulloblastoma formation in conjunction with p53 inactivation.
Main Methods:
- Analysis of genetic lesions in medulloblastoma samples.
- Evaluation of REN (KCTD11) function as a tumor suppressor.
- Assessment of Gli-dependent activation of Hedgehog target genes.
Main Results:
- Allelic deletion of REN (KCTD11) on chromosome 17p13.2 is observed in medulloblastoma.
- Loss of REN (KCTD11) leads to reduced growth inhibitory activity.
- Suppression of Gli-dependent Hedgehog target gene activation occurs upon REN (KCTD11) loss.
- 17p deletions, including p53 inactivation, create haploinsufficiency, disrupting Hedgehog signaling checkpoints.
Conclusions:
- REN (KCTD11) acts as a tumor suppressor in medulloblastoma by inhibiting Hedgehog signaling.
- Allelic deletion of REN (KCTD11) contributes to medulloblastoma development.
- Combined genetic alterations on chromosome 17p, including p53 and REN (KCTD11), cooperate to drive medulloblastoma formation through Hedgehog pathway dysregulation.
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