Cancer testis antigens and genomic instability: More than immunology

Jay, A. Tischfield; Reitz, Diedre; Namekawa, Satoshi H.; Heyer, Wolf‐Dietrich

doi:10.1016/j.dnarep.2021.103214

Cited by 20 publications

(18 citation statements)

References 108 publications

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“…The mechanism of the enhanced therapeutic sensitivity and improved prognosis associated with HPV-positive HNSCC is not fully understood [132]. Considering that some CT antigens upregulated in HPV-positive cancers may promote genomic instability [37] and that high expression of SYCP2 or STAG3 correlates with improved survival in HSNCC [142,143], it is conceivable that aberrant CT antigen expression may contribute to tumor chemo-and radiosensitivity. Although published correlations between CT antigen expression and prognosis in HPV-positive HNSCC are limited, because there is precedent that CT antigens can promote nearly all hallmarks of cancer [36] but many, including those upregulated in HPV-positive HNSCC, do not have formally reported oncogenic cellular functions, studying how CT antigens contribute to HPV-mediated oncogenesis is an intriguing field of study that provides a unique opportunity to uncover novel oncogenic mechanisms and reveal potential new drug targets or collateral sensitivities.…”

Section: Discussionmentioning

confidence: 99%

“…Hanahan and Weinberg defined the "Hallmarks of Cancer", a framework for understanding acquired cellular capabilities that enable carcinogenic initiation and progression [36]. While the oncogenic mechanisms of CT antigens have been reviewed elsewhere [9,10,27,37], the following provides examples of how CT antigens are involved in regulating hallmarks of cancer.…”

Section: Hallmarks Of Cancer Co-opted By Ct Antigensmentioning

confidence: 99%

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Role and Clinical Utility of Cancer/Testis Antigens in Head and Neck Squamous Cell Carcinoma

Münger

2021

Cancers

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Cancer/testis (CT) antigens exhibit selective expression predominantly in immunoprivileged tissues in non-pathological contexts but are aberrantly expressed in diverse cancers. Due to their expression pattern, they have historically been attractive targets for immunotherapies. A growing number of studies implicate CT antigens in almost all hallmarks of cancer, suggesting that they may act as cancer drivers. CT antigens are expressed in head and neck squamous cell carcinomas. However, their role in the pathogenesis of these cancers remains poorly studied. Given that CT antigens hold intriguing potential as therapeutic targets and as biomarkers for prognosis and that they can provide novel insights into oncogenic mechanisms, their further study in the context of head and squamous cell carcinoma is warranted.

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Section: Discussionmentioning

confidence: 99%

Section: Hallmarks Of Cancer Co-opted By Ct Antigensmentioning

confidence: 99%

Role and Clinical Utility of Cancer/Testis Antigens in Head and Neck Squamous Cell Carcinoma

Münger

2021

Cancers

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“…This phenomenon is not widely discussed in the fields of epigenetic therapy ( 15 ) or chromosome instability in cancer ( 16 ), even though such a paradigm might uncover some early drivers of genetic alterations in tumors ( 17 – 19 ). Indeed, it is plausible that some germline-specific genes could induce chromosomal instability ( 20 – 22 ), such as chromothripsis ( 23 – 29 ), but experimental evidence for such a hypothesis was lacking.…”

mentioning

confidence: 99%

Ectopic expression of meiotic cohesin generates chromosome instability in cancer cell line

Boukaba

Liu

Ward

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Many tumors express meiotic genes that could potentially drive somatic chromosome instability. While germline cohesin subunits SMC1B, STAG3, and REC8 are widely expressed in many cancers, messenger RNA and protein for RAD21L subunit are expressed at very low levels. To elucidate the potential of meiotic cohesins to contribute to genome instability, their expression was investigated in human cell lines, predominately in DLD-1. While the induction of the REC8 complex resulted in a mild mitotic phenotype, the expression of the RAD21L complex produced an arrested but viable cell pool, thus providing a source of DNA damage, mitotic chromosome missegregation, sporadic polyteny, and altered gene expression. We also found that genomic binding profiles of ectopically expressed meiotic cohesin complexes were reminiscent of their corresponding specific binding patterns in testis. Furthermore, meiotic cohesins were found to localize to the same sites as BORIS/CTCFL, rather than CTCF sites normally associated with the somatic cohesin complex. These findings highlight the existence of a germline epigenomic memory that is conserved in cells that normally do not express meiotic genes. Our results reveal a mechanism of action by unduly expressed meiotic cohesins that potentially links them to aneuploidy and chromosomal mutations in affected cells.

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“…While the oncogenic mechanisms of CT antigens have been reviewed elsewhere [10,18,22,38], the following provides examples of how CT antigens are involved in regulating hallmarks of cancer.…”

Section: Hallmarks Of Cancer Co-opted By Ct Antigensmentioning

confidence: 99%

Role and Clinical Utility of Cancer/Testis Antigens in Head and Neck Squamous Cell Carcinoma

Wu¹,

Münger²

2021

Preprint

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Cancer/testis (CT) antigens exhibit selective expression predominantly in immunoprivileged tissues in non-pathological contexts but are aberrantly expressed in diverse cancers. Because of their expression pattern, they have historically been attractive targets for immunotherapies. The investigation of mechanistic roles of CT antigens in promoting oncogenesis has historically been a prominent research question, and a growing number of studies implicate CT antigens in promoting almost all the hallmarks of cancer. This suggests that CT antigens may act as cancer drivers. CT antigens are expressed in head and neck squamous cell carcinomas, although their role in the pathogenesis, prognostication, and treatment for this family of cancers remains poorly studied. Given that CT antigens hold intriguing potential as therapeutic targets and as biomarkers for prognosis and therapeutic response and that they can provide novel insights into oncogenic mechanisms, their further study in the context of head and squamous cell carcinoma is warranted.

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Cancer testis antigens and genomic instability: More than immunology

Cited by 20 publications

References 108 publications

Role and Clinical Utility of Cancer/Testis Antigens in Head and Neck Squamous Cell Carcinoma

Role and Clinical Utility of Cancer/Testis Antigens in Head and Neck Squamous Cell Carcinoma

Ectopic expression of meiotic cohesin generates chromosome instability in cancer cell line

Role and Clinical Utility of Cancer/Testis Antigens in Head and Neck Squamous Cell Carcinoma

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