Emerging Contributions of Cancer/Testis Antigens to Neoplastic Behaviors

Gibbs, Zane A.; Whitehurst, Angelique W.

doi:10.1016/j.trecan.2018.08.005

Cited by 98 publications

(96 citation statements)

References 107 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also seemingly consistent with an oncogenic function for POTEs is our observation that several distinct cancer epigenetic alterations each promote POTE expression. Finally, recent data shows that other CTAs promote oncogenic phenotypes [28,31,34,35]. Future studies will examine the role of POTEs in EOC and other cancers, and their potential as therapeutic targets.…”

Section: Discussionmentioning

confidence: 95%

See 1 more Smart Citation

Epigenetic activation of POTE genes in ovarian cancer

et al. 2019

View full text Add to dashboard Cite

The POTE gene family consists of 14 homologous genes localized to autosomal pericentromeres, and a subset of POTEs are cancer-testis antigen (CTA) genes. POTEs are over-expressed in epithelial ovarian cancer (EOC), including the high-grade serous subtype (HGSC), and expression of individual POTEs correlates with chemoresistance and reduced survival in HGSC. The mechanisms driving POTE overexpression in EOC and other cancers is unknown. Here, we investigated the role of epigenetics in regulating POTE expression, with a focus on DNA hypomethylation. Consistent with their pericentromeric localization, Pan-POTE expression in EOC correlated with expression of the pericentromeric repeat NBL2, which was not the case for non-pericentromeric CTAs. POTE genomic regions contain LINE-1 (L1) sequences, and Pan-POTE expression correlated with both global and POTE-specific L1 hypomethylation in EOC. Analysis of individual POTEs using RNA-seq and DNA methylome data from fallopian tube epithelia (FTE) and HGSC revealed that POTEs C, E, and F have increased expression in HGSC in conjunction with DNA hypomethylation at 5' promoter or enhancer regions. Moreover, POTEs C/E/F showed additional increased expression in recurrent HGSC in conjunction with 5' hypomethylation, using patient-matched samples. Experiments using decitabine treatment and DNMT knockout cell lines verified a functional contribution of DNA methylation to POTE repression, and epigenetic drug combinations targeting histone deacetylases (HDACs) and histone methyltransferases (HMTs) in combination with decitabine further increased POTE expression. In summary, several alterations of the cancer epigenome, including pericentromeric activation, global and locus-specific L1 hypomethylation, and locus-specific 5' CpG hypomethylation, converge to promote POTE expression in ovarian cancer.

show abstract

Section: Discussionmentioning

confidence: 95%

“…A recent report suggests that CTA expression correlates with a beneficial clinical response to anti-PD1 immune checkpoint therapy [21]. Notably, CTAs have additional importance in cancer biology because they promote oncogenic phenotypes [22][23][24][25][26][27][28][29][30][31][32][33][34][35].…”

Section: Introductionmentioning

confidence: 99%

Epigenetic activation of POTE genes in ovarian cancer

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Cancer/testis (CT) genes are a class of gene that has expression normally restricted to the testis of adult males, but which become active in some, if not even all cancers (Simpson et al ., ; Whitehurst, ; Gibbs & Whitehurst, ). SPO11, the key mediator of meiotic DSB formation, and PRDM9, the histone methyltransferase activator of a subgroup of meiotic recombination hotspots, are both encoded for by meiosis‐specific genes that have been reported to be CT genes (Koslowski et al ., ; Feichtinger et al ., ).…”

Section: Activation Of Meiotic Chromosome Regulators In Non‐germ Cellmentioning

confidence: 99%

Meiotic gene activation in somatic and germ cell tumours

Feichtinger

McFarlane

2019

Andrology

View full text Add to dashboard Cite

Background Germ cell tumours are uniquely associated with the gametogenic tissues of males and females. A feature of these cancers is that they can express genes that are normally tightly restricted to meiotic cells. This aberrant gene expression has been used as an indicator that these cancer cells are attempting a programmed germ line event, meiotic entry. However, work in non‐germ cell cancers has also indicated that meiotic genes can become aberrantly activated in a wide range of cancer types and indeed provide functions that serve as oncogenic drivers. Here, we review the activation of meiotic factors in cancers and explore commonalities between meiotic gene activation in germ cell and non‐germ cell cancers. Objectives The objectives of this review are to highlight key questions relating to meiotic gene activation in germ cell tumours and to offer possible interpretations as to the biological relevance in this unique cancer type. Materials and Methods PubMed and the GEPIA database were searched for papers in English and for cancer gene expression data, respectively. Results We provide a brief overview of meiotic progression, with a focus on the unique mechanisms of reductional chromosome segregation in meiosis I. We then offer detailed insight into the role of meiotic chromosome regulators in non‐germ cell cancers and extend this to provide an overview of how this might relate to germ cell tumours. Conclusions We propose that meiotic gene activation in germ cell tumours might not indicate an unscheduled attempt to enter a full meiotic programme. Rather, it might simply reflect either aberrant activation of a subset of meiotic genes, with little or no biological relevance, or aberrant activation of a subset of meiotic genes as positive tumour evolutionary/oncogenic drivers. These postulates provide the provocation for further studies in this emerging field.

show abstract

“…It has been over 100 years since the similarity between gametogenesis and tumorigeneses being noticed by oncologist, as multiple characteristics were shared during these two processes, from the immortalization of primordial germ cell to the apoptosis inhibition of oncotransformed cells, from the immune evasion that happened in testis to that in cancer cells. Nowadays, 30 years after the discovery of the first cancer and testis shared antigen, it has been a consensus that cancer/testis antigen affects tumor behaviors and could be a risky factor for poor prognosis (1,2).…”

Section: Introductionmentioning

confidence: 99%

Detecting Melanoma Antigen Family A3 Expression in Solid/Non-Solid Human Tumor

Jiang

Han

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: MAGEA3 is a member of melanoma antigen family and has been recognized to express in many types of human cancers recently. In spite of the development of cancer vaccine, the prognostic value of MAGEA3 has not been well evaluated, due to the variability of clinical data and lack of clinical trials on the prognostic values.Method: Studies that evaluated MAGEA3 expression with a follow-up for at least 36 months were selected by searching in PubMed, WOS, Cochrane library, Embase. Published data was recorded and calculated into odds ratios (OR) for mortality in three or five years with Mantel-Haenszel random-effect model. Results: 11 studies were selected. The median positive rate was 45%. MAGEA3 always combines with worse survival on three or five years survival. The correlation between MAGEA3 and squamous carcinoma seemed stronger than adenocarcinoma on three-year OS while things got a reverse when it came to five-year OS. Most importantly, we found that all solid tumors originated from endoderm seemed to enjoy a strongest correlation among all the three germ layers.Conclusion: In this meta-analysis, we found that the expression of MAGEA3 can connect with worse outcome, and it probably can be a predictor for patients’ prognosis in clinical practice.

show abstract

Emerging Contributions of Cancer/Testis Antigens to Neoplastic Behaviors

Cited by 98 publications

References 107 publications

Epigenetic activation of POTE genes in ovarian cancer

Epigenetic activation of POTE genes in ovarian cancer

Meiotic gene activation in somatic and germ cell tumours

Detecting Melanoma Antigen Family A3 Expression in Solid/Non-Solid Human Tumor

Contact Info

Product

Resources

About