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Primitive neuroectodermal tumor of the midbrain in a murine model of retinoblastoma
D M Marcus1, J L Carpenter, J M O'Brien
1David G. Cogan Eye Pathology Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston 02114.
Abstract:
The first heritable model of retinoblastoma was established by retina-specific expression of simian virus 40 T-antigen (SV40 T-ag) in transgenic mice. Bilateral, multifocal ocular tumors were observed in 100% of transgene-bearing mice. Central nervous system neoplasms occurred at a lower rate (27%) and represented the murine counterpart of human trilateral retinoblastoma. The authors characterized the transgenic brain tumors and found them to be primitive neuroectodermal tumors (PNET) of the midbrain. Murine brain tumors do not involve the pineal gland and most closely resemble undifferentiated suprasellar or parasellar tumors occasionally observed in human trilateral retinoblastoma. The murine malignancies arose from the subependymal cells of the cerebral aqueduct. Immunohistochemical and ultrastructural examination revealed that the transgenic brain tumors were undifferentiated and lacked all antigens associated with normal murine neuronal, glial, and ependymal cells.
Insights
Researchers created the first heritable retinoblastoma model using transgenic mice. This model accurately mimics human trilateral retinoblastoma, including central nervous system tumors.
Area of Science:
- Oncology
- Genetics
- Neuroscience
Background:
- Retinoblastoma is a pediatric eye cancer.
- Trilateral retinoblastoma involves both eyes and the brain.
- A heritable mouse model for retinoblastoma is needed.
Purpose of the Study:
- To establish the first heritable mouse model of retinoblastoma.
- To characterize the resulting ocular and central nervous system tumors.
- To compare the murine model to human trilateral retinoblastoma.
Main Methods:
- Retina-specific expression of simian virus 40 T-antigen (SV40 T-ag) in transgenic mice.
- Histopathological and immunohistochemical analysis of tumors.
- Ultrastructural examination of tumor cells.
Main Results:
- 100% of transgene-bearing mice developed bilateral, multifocal ocular tumors.
- 27% of mice developed central nervous system neoplasms, resembling human trilateral retinoblastoma.
- Murine brain tumors were primitive neuroectodermal tumors (PNETs) originating from subependymal cells, distinct from the pineal gland.
Conclusions:
- The transgenic mouse model successfully replicates heritable retinoblastoma and aspects of trilateral retinoblastoma.
- This model provides a valuable tool for studying retinoblastoma pathogenesis and treatment.
- The murine PNETs offer insights into undifferentiated suprasellar/parasellar tumors in human trilateral retinoblastoma.