The balanced induction of K-ras codon 12 and 13 mutations in mucosa differs from their ratio in neoplastic tissues

Kraus, Magdalena C.; Seelig, Matthias H.; Linnemann, Ulrich; Berger, Martin R.

doi:10.3892/ijo.29.4.957

Cited by 10 publications

(13 citation statements)

References 16 publications

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“…This hypothesis is supported by our previous finding associating K-ras codon 13 mutations with lymph node involvement, and codon 12 mutations with dissemination into the liver (18,19).…”

Section: Discussionsupporting

confidence: 81%

“…K-ras codon 12 mutated tumor cells spread significantly more often into the liver than K-ras codon 13 mutated tumor cells, which were found more often in lymph node specimens (5,13,14,17). Furthermore, K-ras codon 12 mutations increase in frequency relative to K-ras codon 13 mutations during tumor progression (18,19). With respect to their relative distribution, K-ras codon 12 mutations prevail over codon 13 mutations (20).…”

Section: Introductionmentioning

confidence: 99%

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Disseminated colorectal tumor cells in organs prone to metastasis detected by new double enriched nested-PCR in comparison with recognized assays

Kraus

Linnemann²,

Berger

2011

Oncol Rep

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“…This hypothesis is supported by our previous finding associating K-ras codon 13 mutations with lymph node involvement, and codon 12 mutations with dissemination into the liver (18,19).…”

Section: Discussionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Disseminated colorectal tumor cells in organs prone to metastasis detected by new double enriched nested-PCR in comparison with recognized assays

Kraus

Linnemann²,

Berger

2011

Oncol Rep

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“…-----------------------------------------------------------------------------------------------------finding could be due to either the low number of K-ras codon 13 or B-raf mutations observed, or to the fact that these mutations have a lower impact on the whole tumor, thus resulting in less ERK phosphorylation which was missed when a lysate from the total tumor was used. The latter assumption is related to our previous observation that K-ras codon 12 and 13 mutations arise in comparable frequencies in mucosa tissues but that K-Ras codon 12 mutations prevail over codon 13 mutations in polyps, carcinomas and liver metastasis with a growing imbalance (20).…”

Section: Discussionmentioning

confidence: 91%

Analysis of the K-ras/B-raf/Erk signal cascade, p53 and CMAP as markers for tumor progression in colorectal cancer patients

Georgieva¹,

Krasteva²,

Angelova³

et al. 2008

Oncol Rep

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Abstract. Colorectal cancer patients may succumb to their disease because of local recurrence or formation of metastasis. To develop a prognostic tool for these fatal types of progression, 23 patients with colorectal carcinoma were included in this study for the detection at the time of surgery of the incidence of K-ras, B-raf and p53 mutations, the phosphorylation status of Erk and the expression of cystatin-like metastasis-associated protein (CMAP) in tumor, mucosa and liver samples. Polymerase chain reaction-restriction fragment length polymorphism and PCR-SSCP were used to detect the respective mutations. The results of these assays were complemented by sequencing the K-ras, B-raf and p53 mutations. A multiplex RT-PCR assay was used to detect the CMAP mRNA levels and the phosphorylation status of Erk in tumor samples was assessed by Western blot using a phospho-specific Erk antibody. The carcinomas were classified as stages T4 (70%), T3 (17%), T2 (9%) and T1 (4%) and thus represent a group of advanced colorectal carcinomas. The carcinomas (8 out of 23, 39.1%) were mutated in K-ras codons 12 or 13 and two patients had a B-raf (V599) mutation in their tumor. Of 22 tumors, 11 (50%) were positive for pErk, indicating the activation of the RAS/RAF/ERK signaling pathway. Of the 23 tumors, 13 (65.5%) showed an increased CMAP RNA level. Notably, 10 of these 13 patients have already died and two developed liver metastasis. Mutations in p53 were found in only 6 patients (26%), with 6 being detected in carcinoma, 1 in mucosa and 1 in liver tissue. These alterations were classified as non-sense (n=1), mis-sense (n=2) and frame-shift mutations (n=1) as well as intron polymorphisms (n=5). There was a significant correlation between Erk activation and K-ras codon 12 mutation (p=0.016), but not between K-ras codon 13 or B-raf mutations and Erk activation. Furthermore, there was a significant correlation of each positive marker with tumor stage (p=0.001).

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“…Point mutations in the critical coding sequences of the KRAS gene, identified mainly in codon 12 and 13 [17,18], are observed in approximately 30-45% cases of primary colorectal cancer [19,20]. Constitutive activation of the RAS protein, as a result of mutations in the KRAS gene, leads to stimulation of the signaling pathways (PI3K/PTEN/AKT and RAF/MEK/ ERK) responsible for cell growth, inhibition of apoptosis, differentiation, proliferation of cancer cells, invasion and metastases [21,22].…”

Section: Discussionmentioning

confidence: 99%

Molecular differences in the KRAS gene mutation between a primary tumor and related metastatic sites - case report and a literature review.

Kosakowska¹,

Stec²,

Charkiewicz³

et al. 2011

Folia Histochem Cytobiol.

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Abstract:In recent years the the set of diagnostic tools in colorectal cancers has been extended by the assessment of the KRAS gene status. Currently it is a necessary step in order to qualify patients for the targeted therapy. The results of the analysis of several studies revealed a high rate of compliance of the KRAS gene mutational status in primary and metastatic tumors. In this paper we present a rare case of incompatibility of the KRAS mutations in the primary tumor located in the colon and metastatic changes in the liver.

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The balanced induction of K-ras codon 12 and 13 mutations in mucosa differs from their ratio in neoplastic tissues

Cited by 10 publications

References 16 publications

Disseminated colorectal tumor cells in organs prone to metastasis detected by new double enriched nested-PCR in comparison with recognized assays

Disseminated colorectal tumor cells in organs prone to metastasis detected by new double enriched nested-PCR in comparison with recognized assays

Analysis of the K-ras/B-raf/Erk signal cascade, p53 and CMAP as markers for tumor progression in colorectal cancer patients

Molecular differences in the KRAS gene mutation between a primary tumor and related metastatic sites - case report and a literature review.

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