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Updated: Aug 16, 2026
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Search for testicular cancer gene hits dead-end
Angabin Matin1, Joseph H Nadeau
1Department of Molecular Genetics, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. amartin@mdanderson.org
Abstract:
Testicular germ cell tumors (TGCTs) are the first tumors where the cell of origin, and the time of transformation were precisely defined. TGCTs in mice originate from primordial germ cells (PGCs) and develop within the testis during fetal development. TGCTs occur at an appreciable frequency (5%) only in the 129 family of inbred strains of laboratory mice, suggesting strong genetic control. These developmental and genetic properties make the 129 strains an exceptional model system to dissect TGCT pathogenesis. Ter is one of the most potent cancer modifiers genes known; it is a single gene mutation that causes progressive loss of PGCs on all inbred strain backgrounds and dramatically increased susceptibility to spontaneous TGCTs only on the 129 background. We recently showed that inactivation of the Dead end gene causes the Ter phenotype. Sequence analysis of Dead end encoded protein indicates it is homologous to factors involved in gene editing. The identity of Ter as Dead end and its function in PGCs will help clarify the role of editing in PGC biology and elucidate the causes of TGCTs in mice and humans.
Insights
Testicular germ cell tumors (TGCTs) in mice originate from primordial germ cells. The Dead end gene
Area of Science:
- Developmental biology
- Cancer research
- Genetics
Background:
- Testicular germ cell tumors (TGCTs) are precisely defined in origin and transformation time.
- TGCTs in mice originate from fetal primordial germ cells (PGCs) within the testis.
- The 129 inbred mouse strain family exhibits a high frequency (5%) of TGCTs, indicating strong genetic control.
Purpose of the Study:
- To investigate the genetic basis of TGCT pathogenesis using the 129 mouse model.
- To identify the gene responsible for the Ter phenotype, a potent cancer modifier.
- To elucidate the role of the Dead end gene in PGC biology and TGCT development.
Main Methods:
- Genetic analysis of TGCT pathogenesis in 129 mouse strains.
- Characterization of the Ter gene and its role in PGCs.
- Sequence analysis of the Dead end gene and its encoded protein.
Main Results:
- Inactivation of the Dead end gene was shown to cause the Ter phenotype.
- The Dead end gene is identified as the Ter gene.
- The Dead end encoded protein shows homology to gene editing factors.
Conclusions:
- The Dead end gene plays a critical role in PGC biology.
- Gene editing may be involved in PGC development and TGCT pathogenesis.
- Understanding Dead end's function can elucidate causes of TGCTs in mice and humans.
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