Gene Mutations of K- Ras in Gallbladder Mucosae and Gallbladder Carcinoma With An Anomalous Junction of The Pancreaticobiliary Duct

Hanada, Keiji; Tsuchida, Akira; Iwao, Toshiyasu; Eguchi, Naomi; Sasaki, Tamito; Morinaka, Kenji; Mitsudo, Kenji; Kawasaki, Yosuke; Yamamoto, Shigeru; Kajiyama, Goro

doi:10.1111/j.1572-0241.1999.01155.x

Cited by 83 publications

(33 citation statements)

References 17 publications

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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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“…The current study showed a significantly higher incidence of K- ras mutation in GBC, similar to what has been described earlier [21,23,26,27]. This is an expected finding as K- ras mutation occurs late in gallbladder carcinogenesis when it becomes invasive.…”

Section: Discussionsupporting

confidence: 79%

“…These variations possibly suggest different behaviors of this cancer in various high-risk populations. None of the previous studies have found K- ras codon 12 mutations in normal gallbladder mucosa [21,23,26,27]. In the present study, K- ras mutation was detected in a single normal gallbladder tissue sample, which is difficult to explain and suggest that the patient might be at high risk.…”

Section: Discussioncontrasting

confidence: 47%

Prognostic Significance of K-<b><i>ras</i></b> Codon 12 Mutation in Patients with Resected Gallbladder Cancer

et al. 2013

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Background: Point mutation of K-ras is associated with carcinogenesis and overall survival in various cancers. We investigated the mutational spectrum of K-ras codon 12 in resected normal and gallbladder cancer tissue samples in a Northern Indian population and correlated it with different clinicopathological parameters. Patients and Methods: Gallbladder tissues from normal (n = 24) and cancer patients (n = 39) were analyzed for K-ras codon 12 mutation by restriction fragment length polymorphism. Statistical analysis was carried out using the χ² test or Fisher's exact test. Survival was estimated using the Kaplan-Meier method, and the difference between survival curves was analyzed by the log-rank test. Results: The frequency of K-ras mutation was significantly higher (p = 0.001) in gallbladder cancer tissue samples (16/39) compared to normal samples (1/24). Patients with K-ras mutation had a significantly decreased overall survival (p = 0.003), particularly for stage II (p = 0.021) and III (p = 0.009) cancers. No significant correlation was observed with any of the other clinicopathological factors studied. Conclusions: Gallbladder cancer has a high frequency of K-ras codon 12 mutation with poorer outcomes in resected stage II and III disease. K-ras mutational analysis has important prognostic implications that need to be investigated further.

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“…In accordance to a more recent study [21], the most frequent mutation was a G ! T transversion that results in substitution of glycine for valine.…”

Section: K-ras Oncogenesupporting

confidence: 88%

“…It has also been reported that K-ras mutation at codon 12 is associated with early stage gallbladder carcinoma with APBDJ than in that without APBDJ [30].…”

Section: K-ras Oncogenementioning

confidence: 98%

K‐ras, p53 mutations, and microsatellite instability (MSI) in gallbladder cancer

Saetta

2006

Journal of Surgical Oncology

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Despite the considerable progress in understanding the molecular pathology of carcinogenesis, the genetic mechanisms underlying the development and progression of gallbladder cancer (GC) are poorly understood. The survival of GC patients is generally poor. Therefore, it is very useful to define valuable prognostic factors. The most extensively studied oncogenes in gallbladder carcinogenesis are ras, commonly mutated in neoplasms of the gastrointestinal tract. K-ras oncogene is altered in a subset of gallbladder patients and mainly in those having anomalous junction of the pancreaticobiliary tract. Most of the studies of genetic abnormalities in GC have focused on p53 gene. p53 mutation/overexpression and/or LOH is present in more than 50% of gallbladder carcinomas, suggesting an important role in their pathogenesis. However, these results have not any predictive value yet. Moreover, the involvement of an alternative molecular pathway, that of microsatellite instability (MSI), is found in a limited group of GC patients. Additional research is necessary to establish its possible relation to defects of the mismatch repair (MMR) system and its proposed prognostic significance. Further elucidation of the molecular events specific to GC will help to identify novel molecular targets for the diagnosis and clinical management of the patients.

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Gene Mutations of K- Ras in Gallbladder Mucosae and Gallbladder Carcinoma With An Anomalous Junction of The Pancreaticobiliary Duct

Abstract: These results suggest that the specific K-ras mutation in codon 12 (GGT to GAT) may contribute to the early stage of carcinogenesis in the gallbladder with AJPBD.

Cited by 83 publications

References 17 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

Prognostic Significance of K-<b><i>ras</i></b> Codon 12 Mutation in Patients with Resected Gallbladder Cancer

K‐ras, p53 mutations, and microsatellite instability (MSI) in gallbladder cancer

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