Differential diagnosis between chronic pancreatitis and pancreatic cancer: value of the detection of KRAS2 mutations in circulating DNA

Maire, Frédérique; Micard, Stéphanie; Hammel, Pascal; Voitot, Hélène; Lévy, Philippe; Ph, Cugnenc; Ruszniewski, Philippe; Puig, Pierre Laurent

doi:10.1038/sj.bjc.6600475

Cited by 129 publications

(95 citation statements)

References 32 publications

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“…8 In addition, mutant KRAS2 has been detected in pancreatic and duodenal juice from patients with chronic pancreatitis. 11,14,15 This makes it difficult to believe that simple qualitative detection of mutant KRAS2 could be a reliable tool for early diagnosis of pancreatic cancer. However, during cancer progression, cancer cell proliferation and invasion as well as luminal necrosis could result in accumulation of cancer DNA in the pancreatic juice, which may significantly increase the amount of mutant KRAS2 present in the juice of patients with cancer relative to that in patients with pancreatitis.…”

Section: Discussionmentioning

confidence: 99%

“…However, small quantities of mutant KRAS2 can also be detected in pancreatic duct juice from patients with chronic pancreatitis or pancreatic intraepithelial neoplasias (PanINs), which are considered the commonest precursor lesions to invasive pancreatic ductal adenocarcinoma. 8,11,14,15 These studies have not clearly indicated that KRAS2 mutations detected in pancreatic juice are from PanINs. Therefore, while qualitative detection of mutant KRAS2 alone is not an accurate predictor of pancreatic cancer, quantitative assays for KRAS2 mutations in biological fluids might be able to distinguish between pancreatic cancer and other conditions.…”

Section: Research Papermentioning

confidence: 99%

“…Point mutations of the KRAS2 gene at codon 12 have been identified in most pancreatic cancers [6][7][8] and can be detected in pancreatic duct juice, 9 as well as plasma 10,11 and stool. 12, 13 The detection of KRAS2…”

Section: Introductionmentioning

confidence: 99%

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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

Shi

Fukushima

Abe

et al. 2008

Cancer Biology & Therapy

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Research Papermentioning

confidence: 99%

See 1 more Smart Citation

Sensitive and quantitative detection of KRAS2 gene mutations in pancreatic duct juice differentiates patients with pancreatic cancer from chronic pancreatitis, potential for early detection

Shi

Fukushima

Abe

et al. 2008

Cancer Biology & Therapy

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“…Detection of K-ras mutations in circulating DNA has a low sensitivity, but specificity was about 90% for the diagnosis of pancreatic cancer. 17 DNA hypermethylation has been detected in the pancreatic juice of patients with pancreatic ductal adenocarcinoma. 18 However, to our knowledge, there are no published reports pertaining to the detection of aberrant methylation in the plasma DNA of pancreatic cancer patients.…”

mentioning

confidence: 99%

K-ras Mutation and p16 and Preproenkephalin Promoter Hypermethylation in Plasma DNA of Pancreatic Cancer Patients

Jiao

Zhu

Hassan³

et al. 2007

Pancreas

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Objectives-To examine the profiles of K-ras mutations and p16 and preproenkephalin (ppENK) promoter hypermethylation and their associations with cigarette smoking in pancreatic cancer patients.Methods-In plasma DNA of 83 patients with untreated primary pancreatic ductal adenocarcinoma, DNA hypermethylation was determined by methylation-specific polymerase chain reaction and Kras codon 12 mutations by enriched-nested polymerase chain reaction followed by direct sequencing. Information on smoking exposure was collected by in-person interview. Pearson χ 2 test and Fisher exact test were used in statistical analysis.Results-K-ras mutations, ppENK, and p16 promoter hypermethylation were detected in 32.5%, 29.3%, and 24.6% of the patients, respectively. Sixty-three percent (52/83) of patients exhibited at least one of the alterations. Smoking was associated with the presence of K-ras mutations (P = 0.003). A codon 12 G-to-A mutation was predominantly observed in regular smokers and in heavy smokers (pack-year of smoking ≥36). Smoking was not associated with p16 or ppENK hypermethylation.Conclusions-These preliminary observations suggest that plasma DNA might be a useful surrogate in detecting genetic and epigenetic alterations of pancreatic cancer. The findings on the association between K-ras mutation and smoking were in consistency with previous studies. Further studies on environmental modulators of epigenetic changes in pancreatic cancer are warranted.Keywords plasma DNA; K-ras mutation; DNA methylation; p16; preproenkephalin; cigarette smoking; pancreatic cancer Adenocarcinoma of the pancreas is the most common type of pancreatic cancer and is a highly lethal disease among all types of malignancies. 1 The profile of genetic and epigenetic alterations of pancreatic cancer has been unveiled by many studies. 2,3 Because cigarette smoking is a well established risk factor for pancreatic cancer, elucidation of the relationship NIH Public Access Author ManuscriptPancreas. Author manuscript; available in PMC 2007 July 2. Published in final edited form as:Pancreas. 2007 January ; 34(1): 55-62. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript between molecular alterations and such environmental factor will not only advance our understanding on the etiology of pancreatic cancer, but will also have implications for the clinical management of this disease.Mutation activation of the K-ras oncogene is a well established molecular alteration in the pathogenesis of pancreatic ductal adenocarcinoma. 4 Aberrant hypermethylation of 5′ CpG islands of tumor suppressor genes has been identified as an alternative mechanism to mutation or deletion in gene inactivation in different types of cancers. 5 Alteration of the p16 gene, which is responsible for controlling cell growth, has been well characterized in pancreatic carcinogenesis. The p16 is inactivated in approximately 95% of pancreatic adenocarcinomas and approximately 15% of those were attributable to aberrant promoter methylation. 6 The p16 gene ...

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“…[26] Attempts have been made to improve the utility of CA19-9 in differentiating benign from malignant head masses by combining it with other serum markers. Maire et al [33] investigated the value of detecting KRAS2 mutations in circulating DNA for diagnosing malignancy in this setting. The authors concluded that the finding of a normal CA 19-9 level and absence of KRAS2 mutations makes the diagnosis of pancreatic cancer extremely unlikely.…”

Section: Detection Of Pancreatic Cancer In Chronic Pancreatitismentioning

confidence: 99%

Pancreatic Cancer in Chronic Pancreatitis

Dhar

Kalghatgi

Saraf

2015

Indian J Surg Oncol

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Data exists to indicate a definite association between chronic pancreatitis and pancreatic cancer. The strength of this association varies between various causes of pancreatitis, with hereditary and tropical pancreatitis more likely to result in malignancy. Pathogenesis may involve genetic factors, diabetes, smoking and alcohol consumption. Clinically a significant overlap exists between the two conditions, with histology difficult to obtain and interpret in this setting. Biomarkers like CA19-9 and others may be useful, as is a variety of newer imaging modalities. Treatment needs to be individualised as surgery offers the only chance of cure, albeit in but a few.

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Differential diagnosis between chronic pancreatitis and pancreatic cancer: value of the detection of KRAS2 mutations in circulating DNA

Cited by 129 publications

References 32 publications

Sensitive and quantitative detection of KRAS2 gene mutations in pancreatic duct juice differentiates patients with pancreatic cancer from chronic pancreatitis, potential for early detection

Sensitive and quantitative detection of KRAS2 gene mutations in pancreatic duct juice differentiates patients with pancreatic cancer from chronic pancreatitis, potential for early detection

K-ras Mutation and p16 and Preproenkephalin Promoter Hypermethylation in Plasma DNA of Pancreatic Cancer Patients

Pancreatic Cancer in Chronic Pancreatitis

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