Impact of 3′UTR variation patterns of the KRAS gene on the aggressiveness of pancreatobiliary tumors with the KRAS G13D mutation in a Turkish population

Egelí, Ünal; Ak, Seçil; Çeçener, Gülşah; Tunca, Berrin; Tezcan, Gülçin; Sevinc, Elif Demirdogen; Kaya, Ekrem; Dündar, Halit Ziya; Sarkut, Pınar; Ozen, Yilmaz; Balcin, Ozkan; Evrensel, Türkkan; Yerci, Ömer; Uğraş, Nesrin

doi:10.1016/j.pan.2016.05.004

Cited by 2 publications

(2 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Kras codon 13 mutations were reported to have a frequency of ∼7% in pancreatic ductal adenocarcinoma cases ( Buscail et al., 2020b ), including the one (GGC→GAC) shown in this study. Besides our present work, Kras codon 13 mutations were also observed in some other tumor types, such as gastric cancer, lung cancer, colorectal cancer, ovarian cancer, prostate cancer, and pancreatobiliary tumor ( Ayatollahi et al., 2018 ; Egeli et al., 2016 ; Silan et al., 2012 ). A meta-analysis of eight research papers suggests that codon 13 mutations of Kras gene seem to correlate with a worse overall survival of patients with colorectal cancer, but the overall survival is similar to those with Kras wild type in patients receiving anti-EGFR therapy ( Kwak et al., 2017 ).…”

Section: Discussionsupporting

confidence: 74%

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone provokes progression from chronic pancreatitis to pancreatic intraepithelial neoplasia

Chen¹,

Sheng²,

Ma³

et al. 2022

iScience

View full text Add to dashboard Cite

Summary The risk of pancreatic cancer is higher among people who are cigarette smokers than among non-smokers; however, the action mechanisms of cigarette metabolites are not yet fully understood. In this study, we investigated the effect of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in cigarette smoking on chronic pancreatitis and pancreatic cancer as well as the biological mechanism of NNK causing malignant transformation. We show that smoking may promote Kras mutation and P16 promoter methylation from clinical samples and NNK markedly facilitates the growth and migration of pancreatic cancer cells via the activation of Sonic Hedgehog signaling. We demonstrate that NNK promotes acinar-to-ductal metastasis and pancreatic intraepithelial neoplasia in rats with chronic pancreatitis, accompanied by desmoplastic reaction and Gli1 overexpression. Together, we here present evidence that NNK provokes the progression of chronic pancreatitis toward pancreatic cancer and highlight potential strategies and targets for early prevention of pancreatic cancer and its therapeutics.

show abstract

Section: Discussionsupporting

confidence: 74%

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone provokes progression from chronic pancreatitis to pancreatic intraepithelial neoplasia

Chen¹,

Sheng²,

Ma³

et al. 2022

iScience

View full text Add to dashboard Cite

show abstract

“…Pathogenic variant (C>T, 112445441, Gly13Asprs) was repeated in 2 patients; IDs 5 and 16. This mutation (Gly13Asprs) was associated with invasive pancreatobiliary tumors in Turkish population [24]. Pathogenic variant (rs121913529) was also identified in 2 patients; IDs 4 and 11.…”

Section: Kras Pathogenic and Likely Pathogenic Variantsmentioning

confidence: 87%

Genetic Variations of Selected Genes Using Target Deep Sequencing in Colorectal Cancer Patients

Farghal¹,

Saied²,

Ghaith³

et al. 2017

J Cancer Sci Ther

View full text Add to dashboard Cite

Background: Colorectal carcinoma (CRC) is a burden problem in a developing country like Egypt since patients are usually admitted in late stage with bad prognosis and short overall survival. Because of genetic predisposition of CRC and introduction of advanced molecular techniques, efforts are directed to screen for potential pathogenic or disease-causing variants in CRC patients Methods: DNA was isolated from formalin fixed paraffin embedded tissue sections collected from 24 CRC confirmed diagnosed patients. TruSight CRC panel (Illumina) was used for detection of different variants in 15 genes. The generated reads were obtained from Illumina Miseq were clustered into single nucleotide polymorphism (SNPs) and small insertions/deletions (Indels). Further pathogenic variants with somatic and germline mutations were identified according to the recommended criteria. Some CRC patients were subjected to anti-EGFR target therapy.Results: Most of the variants were detected in TP53 gene 140 variants (65%); 105 short deletions none of them was pathogenic, 29 missense mutations and 6 SNPs at splicing sites. Next, ERBB2 has got 17 variants (8.8%) (missense and splicing), 8 of them were damaging disease causing variants. Besides, 16 pathogenic variants were identified in 12 patients (6 in TP53 and 7 in KRAS). Some pathogenic variants were not reported before in CRC e.g. TP53 C>A, rs121912654, Val157Phe. Additionally, patients carried different KRAS wild mutations showed variable response to anti-EGFR target therapy. Conclusion:The most affected pathway in CRC was TP53 pathway followed by ERBB2, NRAS, KRAS and PIK3CA genes. Variable response to target therapy suggested dependence on the type of pathogenic variant identified, also a possible role of ERBB2 which had a significant variant frequency.NRAS. The prevalence rate of TP53 mutation in Arab population is 52.5% compared to 47.5% in matched Western population [7]. TP53 mutations have roles in determining progression, invasiveness and also metastasis of CRC. So, CRC patients with mutant TP53 have more progressive phenotype and poorer survival than those with TP53 wild type [8]. The phosphatidylinositol 3-kinase/Akt/mammalian target of

show abstract

Impact of 3′UTR variation patterns of the KRAS gene on the aggressiveness of pancreatobiliary tumors with the KRAS G13D mutation in a Turkish population

Cited by 2 publications

References 36 publications

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone provokes progression from chronic pancreatitis to pancreatic intraepithelial neoplasia

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone provokes progression from chronic pancreatitis to pancreatic intraepithelial neoplasia

Genetic Variations of Selected Genes Using Target Deep Sequencing in Colorectal Cancer Patients

Contact Info

Product

Resources

About