Detection of point mutation in K-ras oncogene at codon 12 in pancreatic diseases

Ren, Yue-Xin; Xu, Guofan; Li, Zhao‐Shen; Song, Yu-gang

doi:10.3748/wjg.v10.i6.881

Cited by 23 publications

(8 citation statements)

References 27 publications

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“…The only available evidence concerns the prevalence of K-ras mutations in PDA and in chronic pancreatitis (i.e., in the two diseases separately) [41][42][43][44]. In the study by Ren et al [41] the prevalence of K-ras mutations was 79% in tissue specimens of patients with pancreatic carcinoma; such figure was significantly higher in patients with chronic pancreatitis (33%). In pancreatic tissue of 80 patients with chronic pancreatitis examined by Gansauge et al [42], no K-ras mutation was detected.…”

Section: Discussionmentioning

confidence: 95%

Past medical conditions and K-ras mutations in pancreatic ductal adenocarcinoma: a hypothesis-generating study

Crous‐Bou

Porta

Morales

et al. 2008

Cancer Causes Control

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Section: Discussionmentioning

confidence: 95%

Past medical conditions and K-ras mutations in pancreatic ductal adenocarcinoma: a hypothesis-generating study

Crous‐Bou

Porta

Morales

et al. 2008

Cancer Causes Control

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“…In various studies of PDAC, the number of KRASpositive cases varies from 70 to 100% [4,16,36,38,44]. The lower estimates may reflect mutation detection techniques that were not sensitive enough and/or the presence of misclassified tumors in the material.…”

Section: Discussionmentioning

confidence: 95%

Molecular analysis of the EGFR-RAS-RAF pathway in pancreatic ductal adenocarcinomas: lack of mutations in the BRAF and EGFR genes

et al. 2006

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The vast majority of tumors of the pancreas are ductal adenocarcinomas. This cancer type has an extremely poor prognosis and in many Western countries, it represents the fifth leading cause of cancer-related death. Pancreatic ductal adenocarcinomas exhibit the highest incidence of activating KRAS (Ki-Ras) mutations observed in any human cancer. It was therefore of interest to examine how this pattern would relate to mutations in the BRAF and EGFR genes, which are involved in the same signaling pathway as KRAS. We screened a series of 43 formalin-fixed, paraffin-embedded ductal adenocarcinomas of the pancreas. When DNA was extracted from whole tissue sections, KRAS codon 12 mutations were detected in 67% of the tumors. When cancerous ducts were isolated by laser-assisted microdissection, 91% were positive for KRAS mutations. Although it did not reach statistical significance, there was a trend in our material that survival after diagnosis varied according to KRAS mutation subtype, GTT-positive patients having the best prognosis. No alterations in BRAF exons 11 and 15 or in EGFR exons 18-21 were detected in KRAS-positive or KRAS-negative cases. We therefore conclude that the BRAF and EGFR mutations commonly seen in a variety of human cancers are generally absent from pancreatic ductal adenocarcinomas. Apparently, these tumors depend on no more than one genetic hit in the EGFR-RAS-RAF signaling pathway.

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“…For this reason, this mutation has been extensively explored as a potential diagnostic marker 20–23. Unfortunately for use of K-Ras mutations as a diagnostic aid, K-Ras mutations have also been observed in ~30% of samples from patients with CP, although highly variable levels have been reported 24 –27.…”

Section: Previously Observed Relationships Between Chronic Pancreatitmentioning

confidence: 99%

Ras Activity in Acinar Cells Links Chronic Pancreatitis and Pancreatic Cancer

Logsdon

2009

Clinical Gastroenterology and Hepatology

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The relationship between chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) is unclear. CP is a risk factor for PDAC, CP is found within the vicinity of PDAC, and both share many similar genetic alterations. However, it has been long thought that PDAC arises only from duct cells. However, we have recently found that excessive activity within the Ras signaling pathway can lead to acinar cell death or metaplasia and is associated with the development of fibrosis resembling CP and the development of PDAC from acinar cells through the full complement of preneoplastic (pancreatic intraepithelial neoplasia) lesions. Therefore, it is time to reevaluate the relationship between CP and PDAC. We proposed a new model in which Ras activity is the direct link between these 2 diseases. Here we will briefly review the shared properties between CP and PDAC and describe the new model.The nature of the relationship between chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) has always been controversial. Largely this is because PDAC was thought to originate in duct cells, whereas CP clearly develops in acinar cells. However, recently it has become clear that acinar cells can also be a source of PDAC. Furthermore, we have recently found that excessive activity within the Ras signaling pathway can lead to acinar cell death or metaplasia and is associated with the development of fibrosis resembling CP. Therefore, it is time to reevaluate the relationship between these 2 diseases. We have recently proposed a new model in which Ras activity is a direct link between these 2 diseases. 1,2 Here we will briefly review the shared properties between CP and PDAC and describe the new model. A more comprehensive coverage of the same issues will be available later. Chronic Pancreatitis Is a Risk Factor for Pancreatic Ductal AdenocarcinomaCP is a major risk factor for PDAC. 7-10 Although the vast majority of CP patients do not progress to PDAC, the cumulative risk of pancreatic cancer in subjects with CP was reported to be 4% after 20 years, with a standardized incidence ratio of 14. 10 This is at least 10-fold greater risk than for those without CP. For patients with a rare form of CP, hereditary pancreatitis, the risk is even greater at 53 times the normal and a cumulative lifetime risk of 40%, which is the highest of any known genetically associated risk factor. 11 However, the mutations associated with hereditary CP are not observed in PDAC from patients without hereditary CP. 12 Furthermore, the vast majority of patients with CP do not progress to PDAC. Therefore, significant barriers must exist between the mechanisms responsible for CP and the development of PDAC. Both Chronic Pancreatitis and Pancreatic Ductal Adenocarcinoma Possess Preneoplastic LesionsPathologic studies have suggested 2 important precursors to PDAC, pancreatic intraepithelial neoplasias (PanINs) and intraductal papillary mucinous neoplasms. 13,14 PanINs are present in nearly all patients with CP. [15][16][17] It has also bee...

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Detection of point mutation in K-ras oncogene at codon 12 in pancreatic diseases

Cited by 23 publications

References 27 publications

Past medical conditions and K-ras mutations in pancreatic ductal adenocarcinoma: a hypothesis-generating study

Past medical conditions and K-ras mutations in pancreatic ductal adenocarcinoma: a hypothesis-generating study

Molecular analysis of the EGFR-RAS-RAF pathway in pancreatic ductal adenocarcinomas: lack of mutations in the BRAF and EGFR genes

Ras Activity in Acinar Cells Links Chronic Pancreatitis and Pancreatic Cancer

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