Variant Profiling of Candidate Genes in Pancreatic Ductal Adenocarcinoma

Huang, Jiaqi; Löhr, Matthias; Nilsson, Magnus; Segersvärd, Ralf; Matsson, Hans; Verbeke, Caroline S.; Heuchel, Rainer; Kere, Juha; Iafrate, A. John; Zheng, Zongli; Ye, Weimin

doi:10.1373/clinchem.2015.238543

Cited by 21 publications

(16 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Droplet digital PCR (ddPCR) is a next generation digital PCR with greater analytical sensitivity compared to conventional real-time PCR due to an enhanced ability to read nucleic acid at a single molecule level [20]. Viral RNA was extracted from thawed CBM cell pellets (Roche, Basel, Switzerland) and a minimum of 200ug used as template for cDNA synthesis using random primers and M-MLV reverse transcriptase (Promega, Southampton, UK).…”

Section: Methodsmentioning

confidence: 99%

“…After amplification the plate was transferred to the droplet reader to measure the number of positive and negative droplets based on fluorescence amplitude. The number of template molecules per microliter of starting material was estimated by QuantaSoft™ ddPCR software (Bio-Rad, Hercules, US) using an internal Poisson algorithm described previously [20]. …”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Infective respiratory syncytial virus is present in human cord blood samples and most prevalent during winter months

et al. 2017

View full text Add to dashboard Cite

BackgroundHuman respiratory syncytial virus (RSV) remains the most common cause of severe lower respiratory tract disease amongst infants, and continues to cause annual epidemics of respiratory disease every winter worldwide. Demonstrating placental transmission of viable RSV in human samples is a major paradigm shift in respiratory routes considered likely for RSV transmission.MethodsDroplet digital PCR (ddPCR) was used to identify RSV present in cord blood mononucleocytes (CBM). CBMs testing positive for RSV were treated with phytohemagglutinin (PHA), PHA and nitric oxide (NO) or PHA, NO and palivizumab, and co-cultured with HeLa cell monolayers. Subsequent immuno-staining for RSV was used to visualize infective viral plaques.ResultsRSV was detected in 26 of 45 samples (57.7%) by ddPCR. CBM’s collected in winter were more likely to test positive for RSV (17/21 samples, risk = 80%, OR = 7.08; 95% CI 1.80–27.80; p = 0.005) compared to non-winter months (9/24 samples, 37.5%). RSV plaques were observed in non-treated and treated co-cultured HeLa monolayers.ConclusionsDemonstrating active RSV in CBMs suggests in utero transmission of infective virus to the fetus without causing overt disease. This is likely to have an important impact on immune development as well as future virus-host interactions, thereby warranting further investigation.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Infective respiratory syncytial virus is present in human cord blood samples and most prevalent during winter months

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Specific mutations in GNAS and KRAS could predict the progression of intraductal-papillary-mucinous-neoplasmic lesions to pancreas cancer [170], and mutations in KRAS have prognostic value in pancreatic ductal adenocarcinoma [168]. Genomic mutations analysed in 104 triple negative breast cancer cases highlighted the occurrence of frequent alterations in the PI3K pathway and such mutation pattern related to the clinical outcome of patients [151].…”

Section: Cancer Somatic Mutation Analysismentioning

confidence: 99%

Next-Generation Sequencing in Oncology: Genetic Diagnosis, Risk Prediction and Cancer Classification

Kamps

Brandão

Bosch

et al. 2017

IJMS

397

294

View full text Add to dashboard Cite

Next-generation sequencing (NGS) technology has expanded in the last decades with significant improvements in the reliability, sequencing chemistry, pipeline analyses, data interpretation and costs. Such advances make the use of NGS feasible in clinical practice today. This review describes the recent technological developments in NGS applied to the field of oncology. A number of clinical applications are reviewed, i.e., mutation detection in inherited cancer syndromes based on DNA-sequencing, detection of spliceogenic variants based on RNA-sequencing, DNA-sequencing to identify risk modifiers and application for pre-implantation genetic diagnosis, cancer somatic mutation analysis, pharmacogenetics and liquid biopsy. Conclusive remarks, clinical limitations, implications and ethical considerations that relate to the different applications are provided.

show abstract

“…Mutations in KRAS are present in more than 90% of patients ( 14 ) and are known to be related to the initiation of PDAC ( 15 ). Inactivating mutations of TP53 , CDKN2A , and SMAD4 occurred in 15–80% of PDAC patients and 30–75% had mutations in at least two of the four genes ( 16 – 18 ). Several studies ( 19 – 21 ) explored the relationship between driver genes and prognosis and largely found that these genes were associated with disease prognosis.…”

Section: Introductionmentioning

confidence: 99%

STRAP as a New Therapeutic Target for Poor Prognosis of Pancreatic Ductal Adenocarcinoma Patients Mainly Caused by TP53 Mutation

Chen

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

Pancreatic ductal adenocarcinoma (PDAC) has a high mortality rate and poor prognosis. KRAS , TP53 , CDKN2A , and SMAD4 are driver genes of PDAC and 30–75% patients have mutations in at least two of these four genes. Herein, we analyzed the relationship between these genes and prognosis of 762 patients in the absence of coexisting mutations, using data from three independent public datasets. Interestingly, we found that compared with mutations in other driver genes, TP53 mutation plays a significant role in leading to poor prognosis of PDAC. Additionally, we found that snoRNA-mediated rRNA maturation was responsible for the progression of cancer in PDAC patients with TP53 mutations. Inhibition of STRAP, which regulates the localization of SMN complexes and further affects the assembly of snoRNP, can effectively reduce maturation of rRNA and significantly suppress progression of TP53 -mutant or low p53 expression pancreatic cancer cells in vitro and in vivo . Our study highlighted the actual contribution rate of driver genes to patient prognosis, enriching traditional understanding of the relationship between these genes and PDAC. We also provided a possible mechanism and a new target to combat progression of TP53 -mutant PDAC patients.

show abstract

Variant Profiling of Candidate Genes in Pancreatic Ductal Adenocarcinoma

Abstract: BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis. Variant profiling is crucial for developing personalized treatment and elucidating the etiology of this disease.

Cited by 21 publications

References 39 publications

Infective respiratory syncytial virus is present in human cord blood samples and most prevalent during winter months

Infective respiratory syncytial virus is present in human cord blood samples and most prevalent during winter months

Next-Generation Sequencing in Oncology: Genetic Diagnosis, Risk Prediction and Cancer Classification

STRAP as a New Therapeutic Target for Poor Prognosis of Pancreatic Ductal Adenocarcinoma Patients Mainly Caused by TP53 Mutation

Contact Info

Product

Resources

About