Mutation and homozygous deletion of ARHGEF10 in bladder cancer; a candidate tumour suppressor gene at 8p23.3

Williams, Sarah; Taylor, Claire; Platt, Fiona M.; Hurst, Carolyn D.; Aveyard, J S; Knowles, Margaret A.

doi:10.1016/j.cancergencyto.2010.07.053

Cited by 3 publications

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“…To identify further genes of interest, we expanded the cross-species comparison to wider peak regions identified by STAC and GISTIC analyses (Additional file 27 : Table S13). The guanine nucleotide exchange factor family member ARHGEF10 , a candidate tumor suppressor gene (TSG) which has reduced ARHGEF10 expression in > 50% human UC cell lines [ 57 ], was the only gene significantly deleted in all three species, providing further support that ARHGEF10 is an important TSG in UC.…”

Section: Resultsmentioning

confidence: 99%

Cross-species oncogenomics offers insight into human muscle-invasive bladder cancer

Wong,

Abascal,

Ludwig

et al. 2023

Genome Biol

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Background In humans, muscle-invasive bladder cancer (MIBC) is highly aggressive and associated with a poor prognosis. With a high mutation load and large number of altered genes, strategies to delineate key driver events are necessary. Dogs and cats develop urothelial carcinoma (UC) with histological and clinical similarities to human MIBC. Cattle that graze on bracken fern also develop UC, associated with exposure to the carcinogen ptaquiloside. These species may represent relevant animal models of spontaneous and carcinogen-induced UC that can provide insight into human MIBC. Results Whole-exome sequencing of domestic canine (n = 87) and feline (n = 23) UC, and comparative analysis with human MIBC reveals a lower mutation rate in animal cases and the absence of APOBEC mutational signatures. A convergence of driver genes (ARID1A, KDM6A, TP53, FAT1, and NRAS) is discovered, along with common focally amplified and deleted genes involved in regulation of the cell cycle and chromatin remodelling. We identify mismatch repair deficiency in a subset of canine and feline UCs with biallelic inactivation of MSH2. Bovine UC (n = 8) is distinctly different; we identify novel mutational signatures which are recapitulated in vitro in human urinary bladder UC cells treated with bracken fern extracts or purified ptaquiloside. Conclusion Canine and feline urinary bladder UC represent relevant models of MIBC in humans, and cross-species analysis can identify evolutionarily conserved driver genes. We characterize mutational signatures in bovine UC associated with bracken fern and ptaquiloside exposure, a human-linked cancer exposure. Our work demonstrates the relevance of cross-species comparative analysis in understanding both human and animal UC.

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Section: Resultsmentioning

confidence: 99%

Cross-species oncogenomics offers insight into human muscle-invasive bladder cancer

Wong,

Abascal,

Ludwig

et al. 2023

Genome Biol

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“…ARHGEF10 encodes the Rho guanine nucleotide exchange factor, and its role in cancer has not yet been clarified. However, there are studies presenting it as a candidate tumor suppressor gene for pancreatic ductal adenocarcinoma [ 79 ], hepatocellular carcinoma [ 80 ], breast [ 81 ] and urothelial carcinoma [ 82 ]. In addition, while decreased ARHGEF10 expression was observed in tumor cells in these studies, increased ARHGEF10 expression was found in colorectal cancer in our study.…”

Section: Discussionmentioning

confidence: 99%

Multi-Omics Data Analysis Identifies Prognostic Biomarkers across Cancers

Karaman

Işık

2023

Medical Sciences

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Combining omics data from different layers using integrative methods provides a better understanding of the biology of a complex disease such as cancer. The discovery of biomarkers related to cancer development or prognosis helps to find more effective treatment options. This study integrates multi-omics data of different cancer types with a network-based approach to explore common gene modules among different tumors by running community detection methods on the integrated network. The common modules were evaluated by several biological metrics adapted to cancer. Then, a new prognostic scoring method was developed by weighting mRNA expression, methylation, and mutation status of genes. The survival analysis pointed out statistically significant results for GNG11, CBX2, CDKN3, ARHGEF10, CLN8, SEC61G and PTDSS1 genes. The literature search reveals that the identified biomarkers are associated with the same or different types of cancers. Our method does not only identify known cancer-specific biomarker genes, but also proposes new potential biomarkers. Thus, this study provides a rationale for identifying new gene targets and expanding treatment options across cancer types.

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Chromosome 8

Vairamani

Ramalingam

2023

Cancer Genes

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Chromosome 8 spans more than 146 million DNA base pairs, and represents between 4.5 and 5 percent of the total DNA in cells. Sixteen percent of these genes and their mutations have been identified to play a role in cancer development. Cancer is a genetic disease at the somatic cell level. Multiple gene mutations usually precede them throughout one’s life. Oncogenes such as Myc, Lyn, Atad2, etc., from chromosome 8 promoted cancer cell proliferation, invasion, and migration. The increased expression of these proteins can transform a normal cell into a cancer cell. Chromosome 8 also houses multiple tumor suppressor genes, such as Dlc1, E2f5, Gata4, Ido1, etc. These proteins, when expressed, reduce the chances of tumor initiation within cells. Thus, mutations leading to the reduced expression of these genes are associated with multiple cancers. Mutation of other functional genes like Ank1, Ctsb, Ext1, Il7, etc., has also been implicated in various cancers for their role in increasing the invasive nature of cancers by regulating angiogenesis and facilitating cancer metastasis. Cancers can also stem from the translocational mutations of genes in chromosome 8. This chapter explains essential cancer genes, genetic mutations, and gene variations that can cause an increased risk of cancer and its progression.

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Mutation and homozygous deletion of ARHGEF10 in bladder cancer; a candidate tumour suppressor gene at 8p23.3

Cited by 3 publications

References 0 publications

Cross-species oncogenomics offers insight into human muscle-invasive bladder cancer

Cross-species oncogenomics offers insight into human muscle-invasive bladder cancer

Multi-Omics Data Analysis Identifies Prognostic Biomarkers across Cancers

Chromosome 8

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