Related Experiment Video
Updated: Feb 6, 2026
Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
Cross-species genomics identifies DLG2 as a tumor suppressor in osteosarcoma
Yang W Shao1, Geoffrey A Wood2, Jinchang Lu1,3
1Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, M5G 1L7, Canada.
Abstract:
Leveraging the conserved cancer genomes across mammals has the potential to transform driver gene discovery in orphan cancers. Here, we combine cross-species genomics with validation across human-dog-mouse systems to uncover a new bone tumor suppressor gene. Comparative genomics of spontaneous human and dog osteosarcomas (OS) expose Disks Large Homolog 2 (DLG2) as a tumor suppressor candidate. DLG2 copy number loss occurs in 42% of human and 56% of canine OS. Functional validation through pertinent human and canine OS DLG2-deficient cell lines identifies a regulatory role of DLG2 in cell division, migration and tumorigenesis. Moreover, osteoblast-specific deletion of Dlg2 in a clinically relevant genetically engineered mouse model leads to acceleration of OS development, establishing DLG2 as a critical determinant of OS. This widely applicable cross-species approach serves as a platform to expedite the search of cancer drivers in rare human malignancies, offering new targets for cancer therapy.
Insights
Researchers identified Disks Large Homolog 2 (DLG2) as a novel bone tumor suppressor gene. This discovery, using cross-species genomics, offers new therapeutic targets for osteosarcoma.
Area of Science:
- Oncology
- Genomics
- Comparative Medicine
Background:
- Identifying driver genes in rare cancers is challenging.
- Conserved cancer genomes across mammals offer a powerful resource for gene discovery.
Purpose of the Study:
- To uncover novel tumor suppressor genes in osteosarcoma using a cross-species genomics approach.
- To functionally validate the role of candidate genes in osteosarcoma development and progression.
Main Methods:
- Comparative genomic analysis of human and canine osteosarcomas.
- Functional studies in DLG2-deficient human and canine osteosarcoma cell lines.
- In vivo validation using a genetically engineered mouse model with osteoblast-specific Dlg2 deletion.
Main Results:
- Disks Large Homolog 2 (DLG2) was identified as a tumor suppressor candidate through comparative genomics.
- DLG2 copy number loss was observed in 42% of human and 56% of canine osteosarcomas.
- DLG2 deficiency promoted osteosarcoma cell division, migration, and tumorigenesis, and accelerated tumor development in mice.
Conclusions:
- DLG2 is a critical bone tumor suppressor gene in osteosarcoma.
- Cross-species genomics is an effective strategy for discovering cancer driver genes in rare malignancies.
- DLG2 represents a potential new therapeutic target for osteosarcoma treatment.
Related Concept Videos
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:17What is a Species?
02:02Genomics
01:34Crossing Over
The homologous pairs of sister chromosomes—one from the maternal and one from the paternal genome—then begin to align alongside each other lengthwise, matching corresponding DNA positions in a process...
01:39Keystone Species