K-ras point mutations in cancerous and noncancerous biliary epithelium in patients with pancreaticobiliary maljunction

Matsubara, Toshiki; Sakurai, Yoshinori; Sasayama, Yoshinori; Hori, Hideo; Ochiai, Masahiro; Funabiki, Takuzo; Matsumoto, Kazuyuki; Hirono, Iwao

doi:10.1002/(sici)1097-0142(19960415)77:8+<1752::aid-cncr27>3.0.co;2-w

Cited by 31 publications

(47 citation statements)

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“…In contrast, the AUPBD pathway is strongly associated with the K-ras mutation (Funabiki et al, 2009). The reported frequency of the K-ras mutation in GBC with AUPBD ranged from 50 to 83%, whereas the frequency without AUPBD ranged from 0 to 36% (Hanada et al, 1996;Matsubara et al, 1996;Iwase et al, 1997;Hanada et al, 1999). Our results are consistent with these findings, because there were no AUPBD patients among the Bolivian cases, and the frequency of the K-ras mutation in Bolivia was low (1 of 36, 2.8%).…”

Section: Discussionsupporting

confidence: 88%

High Frequency of TP53 but not K-ras Gene Mutations in Bolivian Patients with Gallbladder Cancer

Asai

Loza²,

Roig³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Although genetic characteristics are considered to be a factor influencing the geographic variation in the prevalence of gallbladder cancer (GBC), they have not been well studied in Bolivia, which has a high prevalence rate of GBC. The purpose of this study was to examine the frequency of TP53 and K-ras mutations in Bolivian patients with GBC and to compare them with our previous data obtained in other high-GBC-prevalence countries, namely Japan, Chile, and Hungary. DNA was extracted from cancer sites in paraffin-embedded tissue from 36 patients using a microdissection technique. TP53 mutations at exons 5 to 8 and K-ras mutations at codons 12, 13 and 61 were examined using direct sequencing techniques. The data obtained were compared with those in the other high-GBC-prevalence countries. Of the 36 patients, 18 (50.0%) had a TP53 mutation (one mutation in each of 17 patients and three mutations in one patient), and only one (2.8%) had a K-ras mutation. Of the 20 TP53 mutations, 12 were of the transition type (60.0%). This rate was significantly lower than that in Chile (12/12, P<0.05). In addition, three mutations were of the CpG transition type (15.0%), which is a feature of endogenous mutation. All three were found in the hot spot region of the TP53 gene. In contrast, G:C to T:A transversion was found in Bolivia, suggesting the presence of exogenous carcinogens. Our findings suggest that the development of GBC in Bolivia is associated with both exogenous carcinogens and endogenous mechanisms. The identification of an environmental risk factor for GBC is needed to confirm these findings.

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Section: Discussionsupporting

confidence: 88%

High Frequency of TP53 but not K-ras Gene Mutations in Bolivian Patients with Gallbladder Cancer

Asai

Loza²,

Roig³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…14 Multicentric development of biliary carcinoma may occur in patients with PBM, and mutations of oncogenes, such as K-ras, 15,16 and tumor-suppressing genes, such as p53, 17 are detected in noncancerous biliary epithelium with hyperplasia, metaplasia, and even inflammation before neoplastic changes were histologically detected. In the present case, chronic inflammation of the bile duct due to PBM could first lead to metaplasia, resulting in an increase in the number of Kulchitsky cells that acted as a predisposing factor for the development of neuroendocrine carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Well-Differentiated Endocrine Carcinoma Originating From the Bile Duct in Association With a Congenital Choledochal Cyst

Takahashi

Sasaki

Oshiro

et al. 2013

International Surgery

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We encountered a rare case of a well-differentiated endocrine carcinoma originating from the bile duct in association with a congenital choledochal cyst (CCC). The patient is a 28-year-old woman referred to our clinic for pruritus. Laboratory data showed mild elevation of serum hepatobiliary enzymes. Computed tomography and magnetic resonance imaging demonstrated pancreatobiliary maljunction and a Todani type IV-A CCC from the inferior bile duct to the bilateral intrahepatic bile ducts. A solid tumor was detected in the middle portion of the common bile duct. Pancreatoduodenectomy and total extrahepatic bile duct resection was performed. Based on pathologic and immunohistochemical examinations, a diagnosis of well-differentiated endocrine carcinoma was made according to the World Health Organization criteria. To our knowledge, this is the third report of a neuroendocrine tumor originating from the bile duct in association with a CCC.

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“…With the introduction of translational research methods (e.g. polymerase chain reaction (PCR)), a number of oncogenes, tumor-suppressor genes and apoptotic proteins involved in biliary carcinogenesis have been identified [12][13][14]. Finally, histomorphological studies have provided some evidence, that at least in the gallbladder [15,16] and ampulla of Vater the sequence "intestinal metaplasia-dysplasia-carcinoma" is significant in biliary carcinogenesis [17].…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of biliary carcinogenesis: A pathogenetic multi-stage cascade towards cholangiocarcinoma

1999

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SummaryCarcinomas of the biliary tract are rare cancers developing from the epithelial or blast-like cells lining the bile ducts. A variety of known predisposing factors and recent experimental models of biliary carcinogenesis (e.g., infection with the liver fluke Opisthorchis viverrini, models of chemically induced carcinogenesis and experimental models of pancreaticobiliary maljunction) have elucidated different stages of this complex system of biliary tumorigenesis. Chronic inflammatory processes, generation of active oxygen radicals, altered cellular detoxification mechanisms, activation of oncogenes, functional loss of tumor-suppressor genes and dysregulation of cell proliferation and cell apoptotic mechanisms have been identified as important contributors in the development of cholangiocarcinomas. In this review, the known mechanisms involved in the carcinogenesis of biliary epithelium are addressed. We will divide the topic into four stages: 1) Predisposition and risk factors of biliary cancer. 2) Genotoxic events and alterations leading to specific DNA damage and mutation patterns. 3) Dysregulation of DNA repair mechanisms and apoptosis, permitting survival of mutated cells and 4) Morphological evolution from premalignant biliary lesions to cholangiocarcinoma. Finally, established and hypothetical future therapeutic strategies directed towards specific pathogenetic events during biliary carcinogenesis will be addressed.

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K-ras point mutations in cancerous and noncancerous biliary epithelium in patients with pancreaticobiliary maljunction

Abstract: BACKGROUND. Pancreaticobiliary maljunction (PBM), an anomalous union of the

Cited by 31 publications

References 0 publications

High Frequency of TP53 but not K-ras Gene Mutations in Bolivian Patients with Gallbladder Cancer

High Frequency of TP53 but not K-ras Gene Mutations in Bolivian Patients with Gallbladder Cancer

Well-Differentiated Endocrine Carcinoma Originating From the Bile Duct in Association With a Congenital Choledochal Cyst

Mechanisms of biliary carcinogenesis: A pathogenetic multi-stage cascade towards cholangiocarcinoma

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