Bilateral Germ Cell Tumor of the Testis: Biological and Clinical Implications for a Stem Versus Genetic Origin of Cancers

Jamaal C. Jackson; Darren Sanchez; Aron Y. Joon; Marcos R. Estecio; Andrew C. Johns; Amishi Y. Shah; Matthew Campbell; John F. Ward; Louis L. Pisters; Charles C. Guo; Miao Zhang; Niki M. Zacharias; Shi Ming Tu

doi:10.3390/cells14090658

Bilateral Germ Cell Tumor of the Testis: Biological and Clinical Implications for a Stem Versus Genetic Origin of Cancers

Jamaal C. Jackson, Darren Sanchez, Aron Y. Joon, Marcos R. Estecio, Andrew C. Johns, Amishi Y. Shah, Matthew Campbell, John F. Ward, Louis L. Pisters, Charles C. Guo, Miao Zhang, Niki M. Zacharias, Shi Ming Tu

Research output: Contribution to journal › Article › peer-review

Abstract

Germ cell tumors of the testis (GCTs) provide an ideal tumor model to investigate the cellular versus genetic origin of cancers. In this single institutional study, we evaluated 38 patients with bilateral GCT, including tumors that occurred simultaneously (synchronous) and those occurring at different times (metachronous). For nine of these patients, DNA was isolated from the right and left GCT to determine the genomic and epigenetic differences between tissues using whole-exome sequencing (WES) and reduced representation bisulfite sequencing (RRBS). We found that seminomas and non-seminomas are molecularly distinct based on DNA methylation and not due to synchronous or metachronous disease. In addition, we did not observe conservation of genetic mutations in right and left GCT in either synchronous or metachronous disease. Our data suggest a cellular origin for bilateral GCT.

Original language	English (US)
Article number	658
Journal	Cells
Volume	14
Issue number	9
DOIs	https://doi.org/10.3390/cells14090658
State	Published - May 2025
Externally published	Yes

Keywords

bilateral testicular cancer
cancer stem cells
origin of cancers
tumor heterogeneity

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.3390/cells14090658

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Jackson, J. C., Sanchez, D., Joon, A. Y., Estecio, M. R., Johns, A. C., Shah, A. Y., Campbell, M., Ward, J. F., Pisters, L. L., Guo, C. C., Zhang, M., Zacharias, N. M., & Tu, S. M. (2025). Bilateral Germ Cell Tumor of the Testis: Biological and Clinical Implications for a Stem Versus Genetic Origin of Cancers. Cells, 14(9), Article 658. https://doi.org/10.3390/cells14090658

@article{31ac6652ed664a2d89d5246b1e5900eb,

title = "Bilateral Germ Cell Tumor of the Testis: Biological and Clinical Implications for a Stem Versus Genetic Origin of Cancers",

abstract = "Germ cell tumors of the testis (GCTs) provide an ideal tumor model to investigate the cellular versus genetic origin of cancers. In this single institutional study, we evaluated 38 patients with bilateral GCT, including tumors that occurred simultaneously (synchronous) and those occurring at different times (metachronous). For nine of these patients, DNA was isolated from the right and left GCT to determine the genomic and epigenetic differences between tissues using whole-exome sequencing (WES) and reduced representation bisulfite sequencing (RRBS). We found that seminomas and non-seminomas are molecularly distinct based on DNA methylation and not due to synchronous or metachronous disease. In addition, we did not observe conservation of genetic mutations in right and left GCT in either synchronous or metachronous disease. Our data suggest a cellular origin for bilateral GCT.",

keywords = "bilateral testicular cancer, cancer stem cells, origin of cancers, tumor heterogeneity",

author = "Jackson, \{Jamaal C.\} and Darren Sanchez and Joon, \{Aron Y.\} and Estecio, \{Marcos R.\} and Johns, \{Andrew C.\} and Shah, \{Amishi Y.\} and Matthew Campbell and Ward, \{John F.\} and Pisters, \{Louis L.\} and Guo, \{Charles C.\} and Miao Zhang and Zacharias, \{Niki M.\} and Tu, \{Shi Ming\}",

note = "Publisher Copyright: {\textcopyright} 2025 by the authors.",

year = "2025",

month = may,

doi = "10.3390/cells14090658",

language = "English (US)",

volume = "14",

journal = "Cells",

issn = "2073-4409",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "9",

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TY - JOUR

T1 - Bilateral Germ Cell Tumor of the Testis

T2 - Biological and Clinical Implications for a Stem Versus Genetic Origin of Cancers

AU - Jackson, Jamaal C.

AU - Sanchez, Darren

AU - Joon, Aron Y.

AU - Estecio, Marcos R.

AU - Johns, Andrew C.

AU - Shah, Amishi Y.

AU - Campbell, Matthew

AU - Ward, John F.

AU - Pisters, Louis L.

AU - Guo, Charles C.

AU - Zhang, Miao

AU - Zacharias, Niki M.

AU - Tu, Shi Ming

PY - 2025/5

Y1 - 2025/5

N2 - Germ cell tumors of the testis (GCTs) provide an ideal tumor model to investigate the cellular versus genetic origin of cancers. In this single institutional study, we evaluated 38 patients with bilateral GCT, including tumors that occurred simultaneously (synchronous) and those occurring at different times (metachronous). For nine of these patients, DNA was isolated from the right and left GCT to determine the genomic and epigenetic differences between tissues using whole-exome sequencing (WES) and reduced representation bisulfite sequencing (RRBS). We found that seminomas and non-seminomas are molecularly distinct based on DNA methylation and not due to synchronous or metachronous disease. In addition, we did not observe conservation of genetic mutations in right and left GCT in either synchronous or metachronous disease. Our data suggest a cellular origin for bilateral GCT.

AB - Germ cell tumors of the testis (GCTs) provide an ideal tumor model to investigate the cellular versus genetic origin of cancers. In this single institutional study, we evaluated 38 patients with bilateral GCT, including tumors that occurred simultaneously (synchronous) and those occurring at different times (metachronous). For nine of these patients, DNA was isolated from the right and left GCT to determine the genomic and epigenetic differences between tissues using whole-exome sequencing (WES) and reduced representation bisulfite sequencing (RRBS). We found that seminomas and non-seminomas are molecularly distinct based on DNA methylation and not due to synchronous or metachronous disease. In addition, we did not observe conservation of genetic mutations in right and left GCT in either synchronous or metachronous disease. Our data suggest a cellular origin for bilateral GCT.

KW - bilateral testicular cancer

KW - cancer stem cells

KW - origin of cancers

KW - tumor heterogeneity

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DO - 10.3390/cells14090658

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AN - SCOPUS:105005093712

SN - 2073-4409

VL - 14

JO - Cells

JF - Cells

IS - 9

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ER -

Bilateral Germ Cell Tumor of the Testis: Biological and Clinical Implications for a Stem Versus Genetic Origin of Cancers

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Keywords

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