Human embryonic genes re-expressed in cancer cells

Monk, Marilyn; Holding, Cathy

doi:10.1038/sj.onc.1205088

Cited by 320 publications

(226 citation statements)

References 32 publications

(19 reference statements)

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“…48 The reactivation of pluripotency-associated genes has been also observed in various somatic cancer cells. 49 Finally, manipulation in normal stem cells of some self-renewal pathways, such as Oct4, can also lead to cancer. 50 However, it is still unclear whether such tumors arise from 'sick' stem cells or from nonstem (progenitor) cells, which acquire a stem cell-like phenotype during carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiling in human gastric mucosa infected with Helicobacter pylori

et al. 2007

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Pathogenic mechanisms associated with Helicobacter pylori infection enhance susceptibility of the gastric epithelium to carcinogenic conversion. We have characterized the gene expression profiles of gastric biopsies from 69 French Caucasian patients, of which 43 (62%) were infected with H. pylori. The bacterium was detected in 27 of the 42 antral biopsies examined and in 16 of the 27 fundic biopsies. Infected biopsies were selected for the presence of chronic active gastritis, in absence of metaplasia and dysplasia of the gastric mucosa. Infected antral and fundic biopsies exhibited distinct transcriptional responses. Altered responses were linked with: (1) the extent of polymorphonuclear leukocyte infiltration, (2) bacterial density, and (3) the presence of the virulence factors vacA, babA2, and cagA. Robust modulation of transcripts associated with Toll-like receptors, signal transduction, the immune response, apoptosis, and the cell cycle was consistent with expected responses to Gram-negative bacterial infection. Altered expression of interferon-regulated genes (IFITM1, IRF4, STAT6), indicative of major histocompatibility complex (MHC) II-mediated and Th1-specific responses, as well as altered expression of GATA6, have previously been described in precancerous states. Upregulation of genes abundantly expressed in cancer tissues (UBD, CXCL13, LY96, MAPK8, MMP7, RANKL, CCL18) or in stem cells (IFITM1 and WFDC2) may reveal a molecular switch towards a premalignant state in infected tissues. Tissue microarray analysis of a large number of biopsies, which were either positive or negative for the cag-A virulence factor, when compared to each other and to noninfected controls, confirmed observed gene alterations at the protein level, for eight key transcripts. This study provides 'proof-of-principle' data for identifying molecular mechanisms driving H. pylori-associated carcinogenesis before morphological evidence of changes along the neoplastic progression pathway. Modern Pathology (2007) 20, 974-989;

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Section: Discussionmentioning

confidence: 99%

Gene expression profiling in human gastric mucosa infected with Helicobacter pylori

et al. 2007

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“…Recently, it has been observed in cell culture study that a mature epithelial cell acquiring or expressing Oct4, is likely to get transformed to a dysplastic cell as it fails to undergo differentiation (Hochedlinger et al, 2005;Koukourakis et al, 2012), thereby suggesting the critical role of Oct4 in tumorigenesis. Recent studies have shown existence of subpopulations of cells having self renewal capacity and are believed to be the purported cancer stem cells (CSCs) (Monk and Holding, 2001;Xi et al, 2011). The CSCs are believed to undergo uncontrolled proliferation.…”

Section: Introductionmentioning

confidence: 99%

Comparative Analysis of Oct4 in Different Histological Subtypes of Esophageal Squamous Cell Carcinomas in Different Clinical Conditions

Vaiphei¹,

Sinha²,

Kochhar³

2014

Asian Pacific Journal of Cancer Prevention

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“…17,18 Indeed, many CSGs are either virtually not expressed in somatic normal tissues or exclusively expressed in specific lineages such as embryonal and germline tissues. 6,7 This outlier expression discriminates cancer cells from normal somatic cells and may offer a therapeutic window for preferentially targeting cancer cells, e.g. by adoptive T cell therapy.…”

Section: Resultsmentioning

confidence: 99%

“…6,7 This restricted expression pattern increases the likelihood of circulating lymphocytes directed against immunogenic peptides encoded by these CSGs, 7 which can be exploited clinically. In neuroblastoma and Ewing sarcoma, which are aggressive and oligo-mutated pediatric cancers, 8,9 adoptive T cell therapy targeting CSGs has been successfully applied in humanized mouse models 10–13 and patients.…”

Section: Introductionmentioning

confidence: 99%

Systematic identification of cancer-specific MHC-binding peptides with RAVEN

Baldauf¹,

Gerke²,

Kirschner

et al. 2018

OncoImmunology

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Immunotherapy can revolutionize anti-cancer therapy if specific targets are available. Immunogenic peptides encoded by cancer-specific genes (CSGs) may enable targeted immunotherapy, even of oligo-mutated cancers, which lack neo-antigens generated by protein-coding missense mutations. Here, we describe an algorithm and user-friendly software named RAVEN (Rich Analysis of Variable gene Expressions in Numerous tissues) that automatizes the systematic and fast identification of CSG-encoded peptides highly affine to Major Histocompatibility Complexes (MHC) starting from transcriptome data. We applied RAVEN to a dataset assembled from 2,678 simultaneously normalized gene expression microarrays comprising 50 tumor entities, with a focus on oligo-mutated pediatric cancers, and 71 normal tissue types. RAVEN performed a transcriptome-wide scan in each cancer entity for gender-specific CSGs, and identified several established CSGs, but also many novel candidates potentially suitable for targeting multiple cancer types. The specific expression of the most promising CSGs was validated in cancer cell lines and in a comprehensive tissue-microarray. Subsequently, RAVEN identified likely immunogenic CSG-encoded peptides by predicting their affinity to MHCs and excluded sequence identity to abundantly expressed proteins by interrogating the UniProt protein-database. The predicted affinity of selected peptides was validated in T2-cell peptide-binding assays in which many showed binding-kinetics like a very immunogenic influenza control peptide. Collectively, we provide an exquisitely curated catalogue of cancer-specific and highly MHC-affine peptides across 50 cancer types, and a freely available software (https://github.com/JSGerke/RAVENsoftware) to easily apply our algorithm to any gene expression dataset. We anticipate that our peptide libraries and software constitute a rich resource to advance anti-cancer immunotherapy.

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Human embryonic genes re-expressed in cancer cells

Cited by 320 publications

References 32 publications

Gene expression profiling in human gastric mucosa infected with Helicobacter pylori

Gene expression profiling in human gastric mucosa infected with Helicobacter pylori

Comparative Analysis of Oct4 in Different Histological Subtypes of Esophageal Squamous Cell Carcinomas in Different Clinical Conditions

Systematic identification of cancer-specific MHC-binding peptides with RAVEN

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