Ki-ras mutations and prognosis in colorectal cancer

Kressner, Ulf; Bjørheim, Jens; Westring, Sophia; Wahlberg, Siobhan; Påhlman, Lars; Glimelius, Bengt; Lindmark, Gunilla; Lindblom, Annika; Børresen-Dale, Anne Lise

doi:10.1016/s0959-8049(97)10111-3

Cited by 66 publications

(41 citation statements)

References 26 publications

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“…KRAS mutations have been extensively studied in various tumors. Dramatically different mutation frequencies were detected in pancreatic cancer (69-90%), colorectal cancer (32-53%), lung cancer (15-50%) and gallbladder cancer (10-38%) (13)(14)(15)(16)(17)(18)(19). In gastric cancer, the frequency of KRAS ONCOLOGY REPORTS 22: 515-520, 2009 517 Table I.…”

Section: Discussionmentioning

confidence: 99%

Mutation detection of KRAS by high-resolution melting analysis in Chinese with gastric cancer

Liu

Liu²,

Li³

et al. 2009

Oncol Rep

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Abstract. KRAS proteins play an important role in regulating cell functions. A series of studies has revealed that mutations of KRAS are involved in gastric carcinogenesis. However, mutation status of KRAS remains unclear in gastric cancer from Chinese Mainland. It has been proved that KRAS mutation associates with resistance to epidermal growth factor receptor (EGFR) inhibitors. In this study, KRAS mutations were detected in 52 gastric adenocarcinomas from Northern China. High-resolution melting analysis (HRMA) was used and positive samples were confirmed by direct sequencing. Of the 52 cancers, KRAS mutations were found in 5 (9.6%). All cancers with KRAS mutation were from male patients. Frequencies of KRAS mutation were 14.3% (3/21) and 6.5% (2/31) in differentiated and undifferentiated cancers; 25% (1/4) and 8.3% (4/48) in early and advanced wall penetration cancers; and were 13.3% (2/15) and 8.1% (3/37) in without and with lymph node metastasis cancers, respectively. There was no significant correlation between KRAS mutation and clinicopathological features. There were 3 mutation types in the 5 mutations, including 2 G12D, 1 G12V and 2 G13D mutations. All codon 12 mutations were found in patients with lymph node metastasis and at advanced stage, whereas all codon 13 mutations were found in patients without lymph node metastasis and at early stage. These results support KRAS mutation may only be involved in carcinogenesis of partial gastric cancers and the different mutation types of KRAS may take part in development of gastric cancer at different stages. The resistance of partial gastric cancer patients to EGFR inhibitors may be induced by KRAS mutation.

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Section: Discussionmentioning

confidence: 99%

Mutation detection of KRAS by high-resolution melting analysis in Chinese with gastric cancer

Liu

Liu²,

Li³

et al. 2009

Oncol Rep

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“…However, reported prognostic impact of the K-Ras mutations provided inconsistent results (18)(19)(20)(21)(22). A large meta-analysis suggested that the G12V mutation at codon 12 in the K-Ras gene increases the risks of recurrence or death in patients with colorectal cancer (5).…”

Section: Discussionmentioning

confidence: 99%

Different types of K-Ras mutations are conversely associated with overall survival in patients with colorectal cancer

Winder

Mündlein²,

Rhomberg³

et al. 2009

Oncol Rep

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Abstract.A glycine to valine substitution at codon 12 (G12V) in Kirsten-Ras (K-Ras) gene has been associated with reduced overall survival in colorectal cancer patients; however, the effect of other K-Ras mutations than G12V still remains unclear. Therefore, we investigated the role of different K-Ras mutations on overall survival in a homogeneous, large patient cohort with standardized therapy and uniform analysis of K-Ras mutation status. The study included 342 patients with histopathologically proven colorectal cancer. Survival data were provided by the federal agency for statistics in Austria. Occurrence of K-Ras mutations at codons 12, 13 and 61 were determined by capillary sequencing. The overall K-Ras mutation frequency in carcinoma tissue was 28%. Carriers of the G12V mutation at the K-Ras gene showed a significantly decreased overall survival compared to carriers of the wild-type [HR=2.56 (1.15-5.69)]. Other mutations than G12V were associated with better overall survival compared to wild-type [HR=0.44 (0.2-0.99)]. In conclusion, for the first time, our study showed clearly that different types of K-Ras mutations are conversely associated with overall survival in patients with colorectal cancer.

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“…Mutation of the ras proto-oncogene has been detected in various human cancers, including 95% of pancreatic cancers and up to 50% of large bowel adenocarcinomas (19)(20)(21). Mutation of the K-ras oncogene has been found in adenomas measuring <1 cm (10%-15%) as well as in larger adenomas and adenocarcinomas (30%-60%) (22)(23)(24). Therefore, it has been proposed that a mutation of K-ras is likely to represent a hallmark contributing to the transition from intermediate to late adenoma or adenocarcinoma (25).…”

Section: K-ras Proto-oncogenementioning

confidence: 99%

The Angiogenic Switch Molecule, Secreted FGF-Binding Protein, an Indicator of Early Stages of Pancreatic and Colorectal Adenocarcinoma

Tassi

Wellstein

2006

Seminars in Oncology

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Tumor angiogenesis has been related to the initiation as well as progression toward more aggressive behavior of human tumors. We will discuss genetic events underlying the initiation and progression of colorectal and pancreatic adenocarcinoma with a particular focus on the modulation of angiogenesis. A secreted fibroblast growth factor (FGF) binding protein (FGF-BP), which is an extracellular chaperone molecule for FGFs, has been shown to enhance FGF-mediated biochemical and biologic events and to be a crucial rate-limiting factor for tumor-dependent angiogenesis. Histochemical and in situ hybridization studies with archival samples show that FGF-BP is induced early during the initiation of colorectal and pancreatic adenocarcinoma. We will discuss the potential of this secreted protein as a serum marker to identify at-risk subjects.

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Ki-ras mutations and prognosis in colorectal cancer

Cited by 66 publications

References 26 publications

Mutation detection of KRAS by high-resolution melting analysis in Chinese with gastric cancer

Mutation detection of KRAS by high-resolution melting analysis in Chinese with gastric cancer

Different types of K-Ras mutations are conversely associated with overall survival in patients with colorectal cancer

The Angiogenic Switch Molecule, Secreted FGF-Binding Protein, an Indicator of Early Stages of Pancreatic and Colorectal Adenocarcinoma

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