Functional characterization of a chr13q22.1 pancreatic cancer risk locus reveals long-range interaction and allele-specific effects on<i>DIS3</i>expression

Hoskins, Jason W.; Ibrahim, Abdisamad; Emmanuel, Mickey; Manmiller, Sarah; Wu, Yinglun; O'Neill, Michael C.; Jia, Jinping; Collins, Irene; Zhang, Mingfeng; Thomas, Janelle V.; Rost, Lauren; Das, Sudipto; Parikh, Hemang; Haake, Jefferson M.; Matters, Gail L.; Kurtz, Robert C.; Bamlet, William R.; Klein, Alison P.; Wolpin, Brian M.; Yarden, Ronit I.; Wang, Zhaoming; Smith, Jill P.; Andrésson, Þorkell; Petersen, Gloria M.; Ámundadóttir, Laufey T.

doi:10.1093/hmg/ddw300

Cited by 19 publications

(20 citation statements)

References 57 publications

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“…Because let-7 RNAs can silence MYC, RAS, and other mRNAs, Dis3 depletion ultimately results in accumulation of these gene products, potentially explaining correlations observed for Dis3 inactivation and RAS activation in model systems (Snee et al 2016) and MM (Lohr et al 2014). Perhaps consistent with this model, decreased Dis3 expression has been observed for high-risk genotypes associated with pancreatic cancer (Hoskins et al 2016), where activating RAS mutants are common (Eser et al 2014).…”

Section: Proliferation and Differentiationmentioning

confidence: 68%

Targeting RNA for processing or destruction by the eukaryotic RNA exosome and its cofactors

2017

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The eukaryotic RNA exosome is an essential and conserved protein complex that can degrade or process RNA substrates in the 3 ′ -to-5 ′ direction. Since its discovery nearly two decades ago, studies have focused on determining how the exosome, along with associated cofactors, achieves the demanding task of targeting particular RNAs for degradation and/or processing in both the nucleus and cytoplasm. In this review, we highlight recent advances that have illuminated roles for the RNA exosome and its cofactors in specific biological pathways, alongside studies that attempted to dissect these activities through structural and biochemical characterization of nuclear and cytoplasmic RNA exosome complexes.

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Section: Proliferation and Differentiationmentioning

confidence: 68%

Targeting RNA for processing or destruction by the eukaryotic RNA exosome and its cofactors

2017

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“…This creates a cervical microenvironment that is susceptible to persistent infection and carcinogenesis. KLF12 has been linked to several cancers (16)(17)(18)(19), including head and neck cancers (20,21), which are usually associated with hrHPV. A study of HPV integration breakpoints in the human genome showed that a copy of the virus was integrated between KLF5 and KLF12 in HPV-positive SiHa cells (22).…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Association Study of Prevalent and Persistent Cervical High-Risk Human Papillomavirus (HPV) Infection

Adeyemo

Rotimi

Olaniyan

et al. 2020

Preprint

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Background: Genetic factors may influence the susceptibility to high-risk human papillomavirus (hrHPV) infection and persistence. We conducted the first genome-wide association study (GWAS) to identify variants associated with cervical hrHPV infection and persistence.Methods: Participants were 517 Nigerian women evaluated at baseline and 6 months follow-up visits for HPV. HPV was characterized using SPF10/LiPA25. hrHPV infection was positive if at least one carcinogenic HPV genotype was detected in a sample provided at the baseline visit and persistent if at least one carcinogenic HPV genotype was detected in each of the samples provided at the baseline and follow-up visits. Genotyping was done using the Illumina Multi-Ethnic Genotyping Array (MEGA) and imputation was done using the African Genome Resources Haplotype Reference Panel. Association analysis was done for hrHPV infection (125 cases/392 controls) and for persistent hrHPV infection (51 cases/355 controls) under additive genetic models adjusted for age, HIV status and the first principal component (PC) of the genotypes.Results: The mean (±SD) age of the study participants was 38 (±8) years, 48% were HIV negative, 24% were hrHPV positive and 10% had persistent hrHPV infections. No single variant reached genome-wide significance (p < 5 X 10-8). The top three variants associated with hrHPV infections were intronic variants clustered in KLF12 (all OR: 7.06, p =1.43 x 10-6). The top variants associated with cervical hrHPV persistence were in DAP (OR: 6.86, p =7.15 x 10-8), NR5A2 (OR: 3.65, p =2.03 x 10-7) and MIR365-2 (OR: 7.71, p =2.63 x 10-7) gene regions. Conclusions: This exploratory GWAS yielded suggestive candidate risk loci for cervical hrHPV infection and persistence. The identified loci have biological annotation and functional data supporting their role in hrHPV infection and persistence. Given our limited sample size, larger discovery and replication studies are warranted to further characterize the reported associations.

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“…This intergenic SNP maps at 13q22.1 locus, and has been showed to be strongly associated with pancreatic cancer [1,3,37,[41][42][43]. The locus 13q22.1 has other SNPs associated previously with PA, mainly in European and Chinese populations, some studies suggest a potential long-range enhancer activity but mechanisms are still unknown [44].…”

Section: Discussionmentioning

confidence: 99%

Susceptibility Loci for Pancreatic Cancer in the Brazilian Population

Aoki

Stein

Oliveira

et al. 2020

Preprint

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Background: Pancreatic adenocarcinoma (PA) is a very aggressive cancer and has one of the poorest prognoses. Usually the diagnosis is late and resistant to conventional treatment. Environmental and genetic factors contribute to the etiology, such as tobacco and alcohol consumption, chronic pancreatitis, diabetes and obesity. Somatic mutation in pancreatic cancer cells are known and SNP profile by GWAS could access novel genetic risk factors for this disease in different population context. Here we describe a SNP panel for Brazilian pancreatic cancer, together with clinical and epidemiological data. Methods: 78 pancreatic adenocarcinoma and 256 non-pancreatic cancer subjects had 25 somatic SNP genotyped by real-time PCR. Unconditional logistic regression methods were used to assess the main effects on PA risk, using allelic, co-dominant and dominant inheritance models. Results: 9 SNPs were nominally associated with pancreatic adenocarcinoma risk, with 5 of the minor allele conferring protective effect while 4 related as risk factor. In epidemiological and clinical data, tobacco, diabetes and pancreatitis history were significant related to pancreatic adenocarcinoma risk. Conclusion: We could assess for the first time some SNPs related with PA in Brazilian populations, a result that could be used for genetic screening in risk population such as familial pancreatic cancer, smokers, alcohol users and diabetes patients.

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Functional characterization of a chr13q22.1 pancreatic cancer risk locus reveals long-range interaction and allele-specific effects onDIS3expression

Cited by 19 publications

References 57 publications

Targeting RNA for processing or destruction by the eukaryotic RNA exosome and its cofactors

Targeting RNA for processing or destruction by the eukaryotic RNA exosome and its cofactors

Genome-Wide Association Study of Prevalent and Persistent Cervical High-Risk Human Papillomavirus (HPV) Infection

Susceptibility Loci for Pancreatic Cancer in the Brazilian Population

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