Arid1a: A Gatekeeper in the Development of Pancreatic Cancer From a Rare Precursor Lesion

Li, Mingyang

doi:10.1053/j.gastro.2022.05.046

Cited by 3 publications

(2 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This loss promotes epithelial-mesenchymal transition in human pancreatic cells and sensitizes human pancreatic cancer xenografts to treatment with HSP90 inhibitor NVP-AUY922, by destabilizing client protein vimentin, which is upregulated in ARID1A null cells (50). Decreased activity of ARID1A is required for development of pre-cancerous lesions in the pancreas, including pancreatic intraepithelial neoplasia, intraductal tubulopapillary neoplasm and IPMN (51). ARID1A as part of the SWI/SNF complex participates in DNA repair, interacting with kinase ATR and promoting ATR activation in double strand breaks and induction of the G2/M DNA damage checkpoint (46).…”

Section: Discussionmentioning

confidence: 99%

Pancreatic adenocarcinomas without KRAS, TP53, CDKN2A and SMAD4 mutations and CDKN2A/CDKN2B copy number alterations: a review of the genomic landscape to unveil therapeutic avenues

Voutsadakis¹,

Digklia²

2023

Chin Clin Oncol

View full text Add to dashboard Cite

Background: Pancreatic adenocarcinoma is one of the cancers with the worst prognosis. The current treatment paradigm based on combination chemotherapy has improved survival over the last decade, but the disease is still fatal in most cases. New therapies exploiting the increasing understanding of the molecular pathology of the disease are needed. Although the disease presents with few recurrent molecular alterations, these represent opportunities for targeted treatments to be developed. However, a minority of cases are devoid of these common alterations. A description of the molecular landscape of this sub-set of pancreatic adenocarcinoma could uncover other molecular lesions present in them that could serve as therapeutic targets.Methods: The sub-set of pancreatic cancers without the common alterations in KRAS, TP53, CDKN2A and SMAD4 has been examined from published and publicly available pancreatic cancer cohorts for determination of their clinical and molecular characteristics. The cBioportal platform was used for this evaluation and the OncoKB knowledgebase was used for determination of the functional significance of discovered mutations.Results: About 5% to 10% of pancreatic adenocarcinomas present without the usual molecular alterations that characterize the disease. These cases tend to be genomically stable and have low prevalence of microsatellite or chromosome instability. Molecular alterations that are observed in pancreatic cancers in lower frequencies than the four most prevalent alterations, such as DNA Damage Response and epigenetic modifier mutations, are still observed in the sub-set without the common alterations and may be pathogenically relevant.Conclusions: Despite the absence of most frequent pancreatic cancer alterations in a sub-set of pancreatic adenocarcinomas, this sub-set possesses other alterations in frequencies similar to the rest of pancreatic cancers. Putative targeting of alterations present is discussed and can serve as the basis for targeted therapies development.

show abstract

Section: Discussionmentioning

confidence: 99%

Pancreatic adenocarcinomas without KRAS, TP53, CDKN2A and SMAD4 mutations and CDKN2A/CDKN2B copy number alterations: a review of the genomic landscape to unveil therapeutic avenues

Voutsadakis¹,

Digklia²

2023

Chin Clin Oncol

View full text Add to dashboard Cite

show abstract

“…Current studies have revealed that the occurrence and progression of PC are associated with genetic mutations, dietary habits, and environmental factors [3,4]. Among them, through the advancements in metagenomic and 16 S ribosomal RNA gene sequencing, researchers have discovered a correlation between GM and pancreatic diseases, including PC [5].…”

Section: Introductionmentioning

confidence: 99%

Causal effect between gut microbiota and pancreatic cancer: a two-sample Mendelian randomization study

Jiang,

Mou,

Wang

et al. 2023

BMC Cancer

Self Cite

View full text Add to dashboard Cite

Background Gut microbiota (GM) comprises a vast and diverse community of microorganisms, and recent studies have highlighted the crucial regulatory roles of various GM and their secreted metabolites in pancreatic cancer (PC). However, the causal relationship between GM and PC has yet to be confirmed. Methods In the present study, we used two-sample Mendelian randomization (MR) analysis to investigate the causal effect between GM and PC, with genome-wide association study (GWAS) from MiBioGen consortium as an exposure factor and PC GWAS data from FinnGen as an outcome factor. Inverse variance weighted (IVW) was used as the primary method for this study. Results At the genus level, we observed that Senegalimassilia (OR: 0.635, 95% CI: 0.403–0.998, P = 0.049) exhibited a protective effect against PC, while Odoribacter (OR:1.899, 95%CI:1.157–3.116, P = 0.011), Ruminiclostridium 9(OR:1.976,95%CI:1.128–3.461, P = 0.017), Ruminococcaceae (UCG011)(OR:1.433, 95%CI:1.072–1.916, P = 0.015), and Streptococcus(OR:1.712, 95%CI:1.071–1.736, P = 0.025) were identified as causative factors for PC. Additionally, sensitivity analysis, Cochran’s Q test, the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO), and MR-Egger regression indicated no heterogeneity, horizontal pleiotropy, or reverse causality between GM and PC. Conclusions Our analysis establishes a causal effect between specific GM and PC, which may provide new insights into the potential pathogenic mechanisms of GM in PC and the assignment of effective therapeutic strategies.

show abstract

Improving the prognosis of pancreatic cancer: insights from epidemiology, genomic alterations, and therapeutic challenges

Jiang,

Zheng,

et al. 2023

Front. Med.

View full text Add to dashboard Cite

Arid1a: A Gatekeeper in the Development of Pancreatic Cancer From a Rare Precursor Lesion

Cited by 3 publications

References 18 publications

Pancreatic adenocarcinomas without KRAS, TP53, CDKN2A and SMAD4 mutations and CDKN2A/CDKN2B copy number alterations: a review of the genomic landscape to unveil therapeutic avenues

Pancreatic adenocarcinomas without KRAS, TP53, CDKN2A and SMAD4 mutations and CDKN2A/CDKN2B copy number alterations: a review of the genomic landscape to unveil therapeutic avenues

Causal effect between gut microbiota and pancreatic cancer: a two-sample Mendelian randomization study

Improving the prognosis of pancreatic cancer: insights from epidemiology, genomic alterations, and therapeutic challenges

Contact Info

Product

Resources

About