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Sensitive and quantitative detection of KRAS2 gene mutations in pancreatic duct juice differentiates patients with pancreatic cancer from chronic pancreatitis, potential for early detection.
Cancer Biol Ther. 2008 Mar; 7(3):353-360.CB

Abstract

KRAS2 gene mutations are found in 75-90% of infiltrating pancreatic ductal adenocarcinomas but can also be present with other nonneoplastic pancreatic diseases. We recently developed a novel sensitive assay for point mutation detection, called "LigAmp", which can detect one mutant molecule in the presence of 10,000 wild-type molecules and can quantify mutant DNA over a wide dynamic range. We analyzed KRAS2 mutations in surgically-collected pancreatic duct juice samples from patients with pancreatic adenocarcinoma (n = 27) and chronic pancreatitis(n = 9). DNA sequencing demonstrated that 17 of the 27 pancreatic cancers harbored KRAS2 mutations at codon 12, including G12D (GGT-->GAT), G12V (GTT), and G12R (CGT). We determined the relative amounts of each KRAS2 mutant by simultaneously quantifying wild-type and mutant KRAS2 DNA. For all pancreatic adenocarcinoma patients, the dominant KRAS2 mutation detected in the pancreatic juice corresponded to that found in the primary cancer. Mutation levels were substantially higher in patients with pancreatic cancer (0.05 to 82% of total KRAS2 molecules) compared to those with chronic pancreatitis (0 to 0.7%). Among patients with mutant KRAS2 positive cancers, all but one (94%) had mutant KRAS2 DNA concentrations of more than 0.5% in their pancreatic juice samples, whereas only 1 of 9(11%) pancreatic juice samples from patients with chronic pancreatitis had more than 0.5% mutant KRAS2 DNA, corresponding to a sensitivity of 94% and a specificity of 89%. LigAmp quantification of mutant KRAS2 in pancreatic juice differentiates pancreatic adenocarcinoma from chronic pancreatitis, and may be a useful early detection tool for pancreatic cancer.

Authors+Show Affiliations

Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18075308

Citation

Shi, Chanjuan, et al. "Sensitive and Quantitative Detection of KRAS2 Gene Mutations in Pancreatic Duct Juice Differentiates Patients With Pancreatic Cancer From Chronic Pancreatitis, Potential for Early Detection." Cancer Biology & Therapy, vol. 7, no. 3, 2008, pp. 353-360.
Shi C, Fukushima N, Abe T, et al. Sensitive and quantitative detection of KRAS2 gene mutations in pancreatic duct juice differentiates patients with pancreatic cancer from chronic pancreatitis, potential for early detection. Cancer Biol Ther. 2008;7(3):353-360.
Shi, C., Fukushima, N., Abe, T., Bian, Y., Hua, L., Wendelburg, B. J., Yeo, C. J., Hruban, R. H., Goggins, M. G., & Eshleman, J. R. (2008). Sensitive and quantitative detection of KRAS2 gene mutations in pancreatic duct juice differentiates patients with pancreatic cancer from chronic pancreatitis, potential for early detection. Cancer Biology & Therapy, 7(3), 353-360.
Shi C, et al. Sensitive and Quantitative Detection of KRAS2 Gene Mutations in Pancreatic Duct Juice Differentiates Patients With Pancreatic Cancer From Chronic Pancreatitis, Potential for Early Detection. Cancer Biol Ther. 2008;7(3):353-360. PubMed PMID: 18075308.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sensitive and quantitative detection of KRAS2 gene mutations in pancreatic duct juice differentiates patients with pancreatic cancer from chronic pancreatitis, potential for early detection. AU - Shi,Chanjuan, AU - Fukushima,Noriyoshi, AU - Abe,Tadayoshi, AU - Bian,Yansong, AU - Hua,Li, AU - Wendelburg,Brian J, AU - Yeo,Charles J, AU - Hruban,Ralph H, AU - Goggins,Michael G, AU - Eshleman,James R, PY - 2007/12/14/pubmed PY - 2008/9/5/medline PY - 2007/12/14/entrez SP - 353 EP - 360 JF - Cancer biology & therapy JO - Cancer Biol Ther VL - 7 IS - 3 N2 - KRAS2 gene mutations are found in 75-90% of infiltrating pancreatic ductal adenocarcinomas but can also be present with other nonneoplastic pancreatic diseases. We recently developed a novel sensitive assay for point mutation detection, called "LigAmp", which can detect one mutant molecule in the presence of 10,000 wild-type molecules and can quantify mutant DNA over a wide dynamic range. We analyzed KRAS2 mutations in surgically-collected pancreatic duct juice samples from patients with pancreatic adenocarcinoma (n = 27) and chronic pancreatitis(n = 9). DNA sequencing demonstrated that 17 of the 27 pancreatic cancers harbored KRAS2 mutations at codon 12, including G12D (GGT-->GAT), G12V (GTT), and G12R (CGT). We determined the relative amounts of each KRAS2 mutant by simultaneously quantifying wild-type and mutant KRAS2 DNA. For all pancreatic adenocarcinoma patients, the dominant KRAS2 mutation detected in the pancreatic juice corresponded to that found in the primary cancer. Mutation levels were substantially higher in patients with pancreatic cancer (0.05 to 82% of total KRAS2 molecules) compared to those with chronic pancreatitis (0 to 0.7%). Among patients with mutant KRAS2 positive cancers, all but one (94%) had mutant KRAS2 DNA concentrations of more than 0.5% in their pancreatic juice samples, whereas only 1 of 9(11%) pancreatic juice samples from patients with chronic pancreatitis had more than 0.5% mutant KRAS2 DNA, corresponding to a sensitivity of 94% and a specificity of 89%. LigAmp quantification of mutant KRAS2 in pancreatic juice differentiates pancreatic adenocarcinoma from chronic pancreatitis, and may be a useful early detection tool for pancreatic cancer. SN - 1555-8576 UR - https://www.unboundmedicine.com/medline/citation/18075308/Sensitive_and_quantitative_detection_of_KRAS2_gene_mutations_in_pancreatic_duct_juice_differentiates_patients_with_pancreatic_cancer_from_chronic_pancreatitis_potential_for_early_detection_ L2 - https://www.tandfonline.com/doi/full/10.4161/cbt.7.3.5362 DB - PRIME DP - Unbound Medicine ER -