This mutation was un-detectable in pancreatic cancer tissue samples (n=65) and pancreatic cell line (n=10) DNA suggesting that pancreatic cancer progression is mainly dependent on the K-Ras mutation.
Frequently reported genome alterations were: the +3q27 and +8q24 mutations of TP53 for esophageal cancer; +20q13 for gastric cancer; -18q22 and +20q12-q13 mutations of APC, TP53 and KRAS for colorectal cancer, and the -18q22 mutation of KRAS and TP53 for pancreatic cancer.
The difference between smokers and nonsmokers was not driven by mutations in known driver genes in pancreatic cancer (KRAS, TP53, CDKN2A/p16, and SMAD4), but instead was predominantly observed in genes mutated at lower frequency.
KRAS2 mutations in human pancreatic acinar-ductal metaplastic lesions are limited to those with PanIN: implications for the human pancreatic cancer cell of origin.
We investigated whether genetic changes (K-Ras mutations) in human pancreatic cancer cell lines altered genomic instability and epigenetic events responding to Ras-mitogen activated protein kinase (MAPK) signaling by characterizing 3 human pancreatic cancer cells lines with and without activating mutations in K-Ras.
In this study, we demonstrate that K-Ras, a frequently altered oncogene in human cancers including pancreatic cancer (about 80%), colon cancer (45%) and lung cancer (45%), suppresses p53.
Endoscopic ultrasound-guided fine-needle aspiration biopsy coupled with KRAS mutation assay to distinguish pancreatic cancer from pseudotumoral chronic pancreatitis.
Activating point mutations in the K-Ras oncogene are among the most common genetic alterations in pancreatic cancer, occurring early in the progression of the disease.
Similarly, a combination of KRAS mutations and chromosomal copy number changes at key pancreatic cancer loci, such as CDK2NA and TP53, was detected in a substantial proportion of the tumor fractions but not in matched stromal fractions from the same sample.
Thirteen of 35 patients with pancreatic cancer (102 plasma samples) with elevated CA 19-9 levels (>35 U/mL) and altered K-ras gene showed significant correlation with elevated CA 19-9 levels (P=0.048).
Our findings identify miR-96 as a potent regulator of KRAS, which may provide a novel therapeutic strategy for treatment of pancreatic cancer and other KRAS-driven cancers.
RalA, RalB, and their major effectors RalBP1 and Sec5 were knocked down by stable expression of short hairpin RNAs in the K-Ras-dependent pancreatic cancer-derived cell line MIA PaCa-2.
In this chapter, we review our experience using the Gal4/UAS system to model KRAS-initiated pancreatic cancer in zebrafish, as well as our early efforts using this system to study the influence of other cooperating oncogenes.
Oncogene-directed increased expression of Nrf2 is a new mechanism for the activation of the Nrf2 antioxidant program, and is evident in primary cells and tissues of mice expressing K-Ras(G12D) and B-Raf(V619E), and in human pancreatic cancer.
Although some of the already clinically explored approaches (particularly EGFR and KRAS targeting) deserve further clinical consideration, by employing more innovative and creative clinical trial designs than the gemcitabine-targeted agent paradigm that has thus far invariably failed, the targeting of emerging and relatively unexplored signaling pathways holds great promise to increase our understanding of the complex molecular biology and to advance the clinical management of pancreatic cancer.
Here we report increased expression of the putative pancreatic stem cell marker DCAMKL-1 in an established KRAS transgenic mouse model of pancreatic cancer and in human pancreatic adenocarcinoma.
K-Ras somatic mutations are a strong predictive biomarker for resistance to epidermal growth factor receptor (EGFR) inhibitors in patients with colorectal and pancreatic cancer.
KRAS mutation was detected in none of the AIP cases and 10/11 PC cases (91%, Pearson χ(2) = 22.16, p < 0.001) or 10/16 PC cases (63%) accounting for PC cases with failed DNA amplification.
We retrospectively studied 136 pancreatic cancer patients with available formalin-fixed paraffin-embedded tumor blocks from 2003 to 2009 to understand the clinical significance of KRAS mutations in pancreatic cancer patients treated with gemcitabine-based chemotherapy.