Genetic changes of p53, K-ras, and microsatellite instability in gallbladder carcinoma in high-incidence areas of Japan and Hungary

Nagahashi, Masayuki; Ajioka, Yoichi; Láng, István; Szentirmay, Zoltán; Kásler, Miklós; Nakadaira, Hiroto; Yokoyama, Naoyuki; Watanabe, Gen; Nishikura, Ken; Wakai, Toshifumi; Shirai, Yoshio; Hatakeyama, Katsuyoshi; Yamamoto, Masahiro

doi:10.3748/wjg.14.70

Cited by 54 publications

(56 citation statements)

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“…Inactivation of the TP53 gene is among the most frequent genetic alterations in human malignancies and is thought to play an important role in the pathogenesis of many malignancies (Greenblatt et al, 1994). Although the reported frequency of TP53 mutation in GBC varies widely (ranging from 31 to 70%), most studies report a frequency greater than 50% (Takagi et al, 1994;Yokoyama et al, 1998a;Moreno et al, 2005;Nagahashi et al, 2008). The frequency of TP53 mutation in this study (50% in Bolivian cases) is comparable with the reported figures.…”

Section: Discussionsupporting

confidence: 79%

“…These findings indicate the possibility that there are common factors in the development of GBC between Bolivian patients and Chilean patients. Our aims, therefore, were 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 (Yokoyama et al, 1998a;Nagahashi et al, 2008), to elucidate the pathogenic mechanisms involved in the development of GBC.…”

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confidence: 99%

“…Most studies have focused on mutations of the TP53 tumor suppressor gene, and abnormalities in the TP53 gene were seen in 31-70% of GBC cases (Takagi et al, 1994;Fujii et al, 1996;Yokoyama et al, 1998a;Moreno et al, 2005;Nagahashi et al, 2008;Rai et al, 2011). Mutations in TP53 play an important role in a variety of kinds of human carcinogenesis, and the characteristics of the mutational spectrum are implicated in the mechanisms of carcinogenesis (Greenblatt et al, 1994).…”

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confidence: 99%

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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: 79%

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confidence: 99%

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confidence: 99%

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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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“…Carcinoma of gallbladder is an aggressive malignancy and usually presenting at an advanced stage. It ranks fifth among the gastrointestinal malignancy [3] . Its incidence steadily increases with age and women are affected two to six time more than men [4] .…”

Section: Introductionmentioning

confidence: 99%

Ki-67 Expression in Premalignant and Malignant lesions of Gallbladder

Singh¹

2017

jmscr

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“…The PCR products of exons 7, 8 and intron 7 of p53 and RT-PCR products of p21 were sequenced directly by Shanghai Sangon Biological Engineering Technology & Services Co,. Ltd. (11). The sequence equipment was ABI PRISM 3730.…”

Section: Introductionmentioning

confidence: 99%

Tumor suppressor gene alterations of spontaneously malignant transformed cells from human embryonic muscle in vitro

Li²,

Zheng³

et al. 2010

Oncol Rep

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Abstract.Recent research has shown that mesenchymal stem cells (MSCs) which were cultured for long time could transform malignantly, the transformation mechanism is not clear yet, it might be associated with the activation of oncogenes and inactivation of tumor suppressor genes. In our initial investigation, we found that the cells arising from human embryonic muscle could spontaneously transform into malignancy in vitro and we obtained 6 immortalized cell lines. In this study, polymerase chain reaction (PCR) was used to assay several tumor suppressor genes of these cell lines, and homozygous deletions within chromosomal band 9p2l including MTAP (methylthioadenosine phosphorylase), p16 and p15 were detected. PCR products of p53 exons 7 and 8 of these novel tumor cell lines were assayed by sequencing, and the results showed high prevalence of mutations in these regions, the mutation rate reached as high as 8% in exon 7 and 14% in exon 8, and all of them were point mutations, the intron 7 changed more significantly, including piece deletion, insertion, frameshift and point mutation, it showed almost no similarity to that of the wt p53 sequence, that was totally different from other p53 mutation data published. All the mutation sequences were identical in 6 cell lines, this suggest that there may be a common mutation mechanism and strong selective advantage in these novel tumor cell lines over long-term culture. In conclusion, our research shows that the inactivation of tumor suppressor genes may play an important role in the process of malignant transformation of embryonic muscle cells in vitro. IntroductionThe development of tumors is generally accepted to be a multistep process in which alterations in oncogenes and tumor suppressor genes play an important role (1,2). The process of carcinogenesis involves the gain of oncogene activity and the loss of tumor suppressor gene function, such as Rb, p53 and cyclin-dependent kinase inhibitor (CDKI) family (3-5). The aberrant gene could interfere in many cell funtions, such as cell proliferation, differentiation and apoptosis. The accumulative mutations constitute the base of cell malignant transformation in gene level. The acquired capabilities of tumor cells include their ability to proliferate continuously ignoring apoptosis or growth-inhibitory signals, generating their own mitogenic signals.At present, the reports on the malignant transformation of human cell in vitro are rare. Recent research has found that mesenchymal stem cells (MSCs) cultured for long time in vitro could lead to malignant transformation, but the mechanism is not very clear. The activation of oncogenes and inactivation of tumor suppressor genes are considered to be one of the mechanisms (6-9). We have found that human embryonic muscle cells which were cultured in vitro longterm could become spontaneously immortalized, and we obtained 6 novel malignant cell lines, this new type of cell lines were named human embryonic muscle-derived malignant transformed cells (hEMTCs). These hEMTCs could be pass...

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Genetic changes of p53, K-ras, and microsatellite instability in gallbladder carcinoma in high-incidence areas of Japan and Hungary

Abstract: It appears that the p53 mutations and MSI differ in patients with gallbladder carcinoma between two distinct high-incidence areas. Geographic variation might exist in the process of gallbladder carcinogenesis.

Cited by 54 publications

References 37 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

Ki-67 Expression in Premalignant and Malignant lesions of Gallbladder

Tumor suppressor gene alterations of spontaneously malignant transformed cells from human embryonic muscle in vitro

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