Ethnic difference in the pattern of K‐ras oncogene mutations in human colorectal cancers

Hayashi, Naoki; Sugai, Sachiko; Ito, Isao; Shoji, Nobuyuki; Ogawa, Michio; Nakamura, Yusuke

doi:10.1002/(sici)1098-1004(1996)8:3<258::aid-humu9>3.3.co;2-5

Cited by 8 publications

(12 citation statements)

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“…[26,32] Consistent with other studies worldwide, our study showed that K-ras codon 13 mutations were less frequent than those of codon 12 (although to variable degrees). [7,8,10,11,18,19,25,30,31] Furthermore, all three codon 13 mutations identified were GGC>GAC (Gly>Asp) mutations, which is consistent with the bulk of the literature showing that this mutation is the predominant in codon 13 in CRC [ Table 3]. This amino acid substitution in codon 13 has been linked to reduced survival rate, less stable cancer and disease relapse and death.…”

Section: Discussionsupporting

confidence: 86%

“…[17][18][19][20] The current study revealed that the G>T transversions and the G>A transitions were equal in frequency and constituted 41.4% each. The latter finding is similar to that reported from neighboring Iran in sporadic CRC, but is in contrast to the bulk of studies from developed countries [7,8,[21][22][23][24][25][26] and some developing countries, [18] where G>A transitions far exceeded G>T transversions. The variation in the pattern of specific alteration observed, i.e.…”

Section: Discussionmentioning

confidence: 99%

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The frequency and spectrum of K-ras mutations among Iraqi patients with sporadic colorectal carcinoma

et al. 2012

Indian J Cancer

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

The frequency and spectrum of K-ras mutations among Iraqi patients with sporadic colorectal carcinoma

et al. 2012

Indian J Cancer

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Section: Discussionmentioning

confidence: 99%

“…Hayashi et al38 indicated that the mutational patterns of K‐ ras gene at codon 12, 13, and 61 are not the same in different populations, though they are the dominant mutations at codons 12 or 13. A possible explanation put forth by Hayashi et al38 was that an environmental carcinogen prevailing in a geographic region combines with the susceptibility of a particular tissue to dictate which type of DNA lesion will predominate. The predominance of G‐to‐A mutations among American and Japanese colorectal cancer patients could be attributable either to alkylating agents or to the absence of direct interaction with any carcinogens 38, 39.…”

Section: Discussionmentioning

confidence: 99%

High frequency of activated K‐ras codon 15 mutant in colorectal carcinomas from Taiwanese patients

Wang

Hsieh

Chen

et al. 2003

Intl Journal of Cancer

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Colorectal carcinogenesis is regarded as a multistep process resulting from accumulation of genetic alterations, including activation of protooncogenes and inactivation of tumor suppressor genes via signal transduction trigger the stage-wise progression to malignancy. The reported incidence of K-ras mutation detected in general tissue samples ranges from 21-60% in primary colorectal cancers (CRC). To assess the prevalence and spectrum of K-ras mutations in Taiwanese patients with CRC, we analyzed 65 CRC patients by polymerase chain reaction-single strand conformation polymorphism analysis, followed by direct sequencing. K-ras mutations were detected in 43.1% (28 of 65) of the tumors. The mutational hot spots were located at codons 12, 13, 15 and 20, especially with the highest frequency at codon 15. To understand whether the codon 15 mutations in CRC were associated with activation of K-ras oncogene and the alterations of its biocharacteristics, mutant K-ras genes were cloned from tumor tissues and then inserted into expression vector pBKCMV to construct the prokaryotic expression plasmid pK15MCMV. Mutant K-ras genes were expressed at high levels in E. coli and the mutant K-ras proteins were shown to be functional with respect to their well-known specific, highaffinity, GDP/GTP binding. The purified K-ras protein from E. coli was then measured for its intrinsic GTPase activity and the extrinsic GTPase activity in the presence of GTPaseactivating protein for ras. We found that the extrinsic GTPase activity of the codon 15 mutant K-ras proteins (p21 K-ras15M ) in the presence of GAP is much lower than that of the wild-type K-ras protein (p21 BN), whereas the intrinsic GTPase activity is nearly the same as that of the wild-type K-ras protein. The results indicated that mutation at the codon 15 of K-ras gene indeed decreased GTPase activity in CRC, however, its association with tumorigenesis of CRC needs be clarified by further studies.

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“…2 3 Mutation within the KRAS2 gene occurs most commonly at positions 1 and 2 of codons 12 and 13. [3][4][5][6] Molecular staging strategies using either immunohistochemistry or reverse transcription polymerase chain reaction (PCR) have shown that approximately 30-40% of patients who were histologically stage II/Dukes' B disease harbour occult micrometastases in the locoregional lymph nodes. [7][8][9][10] Using similar strategies, micrometastases have also been detected in the bone marrow of patients with various gastrointestinal malignancies.…”

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confidence: 99%

A prospective study of circulating mutant KRAS2 in the serum of patients with colorectal neoplasia: strong prognostic indicator in postoperative follow up

Ryan

Lefort²,

McManus³

et al. 2003

Gut

100

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Background and aims: Mutant tumour derived DNA has been detected in the sera of colorectal cancer patients. We investigated if mutant serum KRAS2 was detectable preoperatively in a large group of patients with colorectal neoplasia. A prospective study of 94 patients who underwent putative curative resection for colorectal carcinoma (CRC) was performed to ascertain if serum mutant KRAS2 could be used postoperatively as a disease marker. Methods: Preoperative sera from 78 patients were analysed (group A). Sera from 94 patients were obtained three monthly for up to three years during the postoperative period (group B). Codon 12 and 13 KRAS2 mutations were analysed in matched tumour and serum samples. Results: In the preoperative group (group A), KRAS2 mutation was found in 41/78 (53%) tumours and in 32/78 (41%) preoperative sera. Of 41 tumour KRAS2 mutation positive cases, 31/41 (76%) had an identical serum mutation detectable. In group B, the postoperative follow up group, 60/94 cases were primary tumour KRAS2 mutation positive. Of these 60, 16/60 (27%) became persistently serum mutant KRAS2 positive postoperatively. Ten of 16 (63%) of these developed a recurrence compared with only 1/44 (2%) patients who remained serum mutant negative (odds ratio 71.7 (95% confidence interval 7.7-663.9; p=0.0000). None of 34 tumour mutation negative cases became serum mutant KRAS2 positive postoperatively, despite recurrence in 9/34 patients. The relative hazard of disease recurrence in postoperative serum mutant KRAS2 positive patients was 6.37 (2.26-18.0; p=0.000). Conclusions: Serum mutant KRAS2 can be detected preoperatively in all stages of colorectal neoplasia. Postoperatively, serum mutant KRAS2 is a strong predictor of disease recurrence, stronger even than Dukes' stage of disease, and thus shows potential for use in clinical practice as a marker of preclinical disease recurrence.

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Ethnic difference in the pattern of K‐ras oncogene mutations in human colorectal cancers

Cited by 8 publications

References 0 publications

The frequency and spectrum of K-ras mutations among Iraqi patients with sporadic colorectal carcinoma

The frequency and spectrum of K-ras mutations among Iraqi patients with sporadic colorectal carcinoma

High frequency of activated K‐ras codon 15 mutant in colorectal carcinomas from Taiwanese patients

A prospective study of circulating mutant KRAS2 in the serum of patients with colorectal neoplasia: strong prognostic indicator in postoperative follow up

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