Cross-Species Analysis of Mouse and Human Cancer Genomes

Robles-Espinoza, Carla Daniela; Adams, David J.

doi:10.1101/pdb.top078824

Cited by 7 publications

(5 citation statements)

References 46 publications

(35 reference statements)

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“…As regards an appropriate cancer model, in addition to similar pathological phenotypes it is highly expected that the model also carries comparable molecular features and follows same carcinogenesis progress with its cognate human cancer type 5 . Several investigations focusing on the molecular features of AOM/DSS model were implemented, which reported some common features shared by human and mouse CRC, such as mutation or deregulation of KRAS 6 and CTNNB1 7,8 .…”

Section: Introductionmentioning

confidence: 99%

Genomic variants in mouse model induced by azoxymethane and dextran sodium sulfate improperly mimic human colorectal cancer

Pan

Lou

Zhang

et al. 2017

Sci Rep

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Mouse model induced by azoxymethane (AOM) and dextran sodium sulfate (DSS) is generally accepted as an ideal object to study on the carcinogenesis mechanisms of human colorectal cancer (CRC). The genomic responses to the AOM/DSS treatment in mouse that possibly lead to elucidation of CRC pathological mechanism are still poorly understood. For the first time, we investigated the cancer genome landscape of AOM/DSS mouse model by exome sequencing, to testify its molecular faithfulness to human CRC. Of 14 neoplastic samples, 7575 somatic variants were identified, which resulted in 2507 mutant genes and exhibited a large diversity in both colorectal aberrant crypt foci (ACF) and tumors even those tissues that were gained from the similar morphology or same treatment period. Cross-species comparison of the somatic variants demonstrated the totally different patterns of variable sites, mutant genes and perturbed pathways between mouse and human CRC. We therefore come to a conclusion that the tumorigenesis at genomic level in AOM/DSS model may not be properly comparable with that in human CRC, and the molecular mechanism elicited from this animal model should be carefully evaluated.

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Section: Introductionmentioning

confidence: 99%

Genomic variants in mouse model induced by azoxymethane and dextran sodium sulfate improperly mimic human colorectal cancer

Pan

Lou

Zhang

et al. 2017

Sci Rep

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“…GEMMs are also indispensable in preclinical studies to test new drugs in immunocompetent animals [26]. Thus, cross-species analyses provide a powerful tool to pinpoint genes conserved across both species that are master regulators of tumor development [27][28][29].…”

Section: Introductionmentioning

confidence: 99%

Sulfiredoxin as a Potential Therapeutic Target for Advanced and Metastatic Prostate Cancer

Barquilha

Santos

Monção

et al. 2020

Oxidative Medicine and Cellular Longevity

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The incidence of prostate cancer (PCa) is increasing, and it is currently the second most frequent cause of death by cancer in men. Despite advancements in cancer therapies, new therapeutic approaches are still needed for treatment-refractory advanced metastatic PCa. Cross-species analysis presents a robust strategy for the discovery of new potential therapeutic targets. This strategy involves the integration of genomic data from genetically engineered mouse models (GEMMs) and human PCa datasets. Considering the role of antioxidant pathways in tumor initiation and progression, we searched oxidative stress-related genes for a potential therapeutic target for PCa. First, we analyzed RNA-sequencing data from Pb-Cre4; Ptenf/f mice and discovered an increase in sulfiredoxin (Srxn1) mRNA expression in high-grade prostatic intraepithelial neoplasia (PIN), well-differentiated adenocarcinoma (medium-stage tumors), and poor-differentiated adenocarcinoma (advanced-stage prostate tumors). The increase of SRXN1 protein expression was confirmed by immunohistochemistry in mouse prostate tumor paraffin samples. Analyses of human databases and prostate tissue microarrays demonstrated that SRXN1 is overexpressed in a subset of high-grade prostate tumors and correlates with aggressive PCa with worse prognosis and decreased survival. Analyses in vitro showed that SRXN1 expression is also higher in most PCa cell lines compared to normal cell lines. Furthermore, siRNA-mediated downregulation of SRXN1 led to decreased viability of PCa cells LNCaP. In conclusion, we identified the antioxidant enzyme SRXN1 as a potential therapeutic target for PCa. Our results suggest that the use of specific SRXN1 inhibitors may be an effective strategy for the adjuvant treatment of castration-resistant PCa with SRXN1 overexpression.

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“…A number of genetically engineered mouse models (GEMM) of prostate cancer have been developed, and triangulating the findings from genome-wide expression datasets from human cancers with those from well-characterised mouse models may provide a useful filter to prioritise genes that are functionally important to cancer development (Robles-Espinoza & Adams, 2014). Previous studies in various cancer types have demonstrated that integration of gene expression or copy number alteration data from human and murine tumours is a viable approach to derive diagnostic, prognostic or predictive signatures (Belmont et al, 2014) and to identify candidate driver genes (Ellwood-Yen et al, 2003;Tompkins et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Identification of potential therapeutic targets in prostate cancer through a cross‐species approach

Jurmeister¹,

Ramos-Montoya²,

Sandi³

et al. 2018

EMBO Mol Med

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Genetically engineered mouse models of cancer can be used to filter genome‐wide expression datasets generated from human tumours and to identify gene expression alterations that are functionally important to cancer development and progression. In this study, we have generated RNAseq data from tumours arising in two established mouse models of prostate cancer, PB‐Cre/PtenloxP/loxP and p53loxP/lox PRbloxP/loxP, and integrated this with published human prostate cancer expression data to pinpoint cancer‐associated gene expression changes that are conserved between the two species. To identify potential therapeutic targets, we then filtered this information for genes that are either known or predicted to be druggable. Using this approach, we revealed a functional role for the kinase MELK as a driver and potential therapeutic target in prostate cancer. We found that MELK expression was required for cell survival, affected the expression of genes associated with prostate cancer progression and was associated with biochemical recurrence.

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Cross-Species Analysis of Mouse and Human Cancer Genomes

Cited by 7 publications

References 46 publications

Genomic variants in mouse model induced by azoxymethane and dextran sodium sulfate improperly mimic human colorectal cancer

Genomic variants in mouse model induced by azoxymethane and dextran sodium sulfate improperly mimic human colorectal cancer

Sulfiredoxin as a Potential Therapeutic Target for Advanced and Metastatic Prostate Cancer

Identification of potential therapeutic targets in prostate cancer through a cross‐species approach

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