ras gene mutations in colorectal cancer

AbstractDue to increased colorectal cancer incidence there is a necessity of seeking new both prognostic and prediction factors that will allow to evolve new diagnostic tests. K-ras gene seems to be such a factor and its mutations are considered to be an early marker of progression of colorectal cancer.was to find a correlation between K-ras gene mutation in patients with diagnosed colorectal cancer and selected clinical parameters.A total of 104 patients (41 women and 63 men) with diagnosed colorectal cancer were included in this study. The average age of male group was 68.3 and in female group − 65.9. Samples were taken from paraffine blocks with tissue from diagnosed patients and K-ras gene mutation were identified. Afterwards the statistical analysis was made seeking the correlation between K-ras gene mutation incidence and clinical TNM staging system, tumour localisation, histological type, sex, age.K-ras gene mutations were detected in 20.1% of all colorectal cancers. Significantly higher rate of K-ras gene mutations were diagnosed among patients classified at stage I (40%), stage IIC (50%) and stage IV (50%) according to the TNM classification.The results of our study are compatible with other studies and indicate the correlation between K-ras gene mutation and colorectal cancer incidence. Identification of K-ras gene mutation may complement other diagnostic methods at early stage of colorectal cancer.

Download Full-text

Prognostic and Predictive Value of RAS Gene Mutations in Colorectal Cancer: Moving Beyond KRAS Exon 2

Drugs ◽

10.1007/s40265-015-0459-x ◽

2015 ◽

Vol 75 (15) ◽

pp. 1739-1756 ◽

Cited By ~ 6

Author(s):

Nele Boeckx ◽

Marc Peeters ◽

Guy Van Camp ◽

Patrick Pauwels ◽

Ken Op de Beeck ◽

...

Keyword(s):

Colorectal Cancer ◽

Predictive Value ◽

Gene Mutations ◽

Ras Gene ◽

Exon 2 ◽

Kras Exon

Download Full-text

K-RAS Mutation Profile in Puerto Rican Patients with Colorectal Cancer: Trends from April 2009 to January 2011

The International Journal of Biological Markers ◽

10.5301/jbm.5000043 ◽

2013 ◽

Vol 28 (4) ◽

pp. 393-397 ◽

Cited By ~ 2

Author(s):

Yelitza Ruiz-Candelaria ◽

Christine Miranda-Diaz ◽

Robert F. Hunter-Mellado

Keyword(s):

Colorectal Cancer ◽

Puerto Rican ◽

Cancer Patients ◽

Cancer Survival ◽

Gene Mutations ◽

Common Mutation ◽

Ras Gene ◽

Ras Mutations ◽

Predictors Of Response ◽

Colorectal Cancer Patients

The frequency of K-RAS mutations ranges between 30% and 48% among the Caucasian, Asian, and European populations and these mutations are predictors of response to EGFR therapies. We sought to determine the expression of K-RAS gene mutations among colorectal cancer patients in PuertoRico. A retrospective study was conducted to determine the expression of mutant K-RAS among colorectal cancer patients in Puerto Rico between April 2009 and January 2011. The mutant expression of K-RAS was found in 39% (n=195) of the Puerto Rican population, and was more common in the age group of 51-69 years (53.8%) and in males (55.4%, p>0.05). Moreover, mutant K-RAS was more commonly found in tumors of the proximal area (43.8%; p=0.03), with distant metastasis (43.3%, p=0.018), with a mucinous histotype (31.7% p>0.05), and in ulcerated tumors (38.8%, p>0.05). K-RAS mutations were observed on codon 12 (87.7%) and codon 13 (12.3%). The most frequent mutation on codon 12 was 12 ASP (39.5%), followed by 12 VAL (25.4%) that is associated with a significant decrease in overall cancer survival. The mutant expression of K-RAS in cases of rectum carcinoma was 39.5%, where the most common mutation was 12 VAL (37.5%). The frequency of K-RAS mutations in the Puerto Rican population here studied was 39% and mutant K-RAS was associated with advanced colorectal cancer stage, mucinous histotype, and ulcerated tumors.

Download Full-text

An Analysis of Relationship Between RAS Mutations and Prognosis of Primary Tumour Resection for Metastatic Colorectal Cancer Patients

Cellular Physiology and Biochemistry ◽

10.1159/000494242 ◽

2018 ◽

Vol 50 (2) ◽

pp. 768-782

Author(s):

Li Liang ◽

Jiawen Tian ◽

Yiyi Yu ◽

Zhiming Wang ◽

Ke Peng ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Metastatic Colorectal Cancer ◽

Survival Time ◽

Primary Tumour ◽

Gene Mutations ◽

Tumour Resection ◽

Ras Gene ◽

The Impact ◽

Primary Tumour Resection

Background/Aims: Non-radical primary tumour resection (PTR) of asymptomatic metastatic colorectal cancer (mCRC) can prolong survival time of some patients. Patients with mutated RAS gene have worse survival outcome. This study aimed to investigate the impact of RAS gene mutations on the prognosis of asymptomatic unresectable mCRC patients who underwent PTR. Methods: A retrospective observational cohort study was deduced among mCRC patients who experienced PTR or had intact primary tumour (IPT). All of them had the primary tumour tissue genotyping tested for RAS (KRAS and NRAS) gene mutations. The tumour-related overall survival (OS) time and progression-free survival (PFS) time was estimated. From January 2011 to June 2014, 421 mCRC patients with asymptomatic, unresectable, metastatic disease were enrolled in this study. Among them, 282 patients underwent PTR and 139 patients had IPT. Results: The mutation rate of RAS was 53.8% (221/411). With a median followed-up time of 46.5 months, the overall survival time of mCRC patients harboring wtRAS or mtRAS was 28.0 versus 22.0 months (p = 0.043) in PTR group and was 21.6 versus 17.8 months (p=0.071) in IPT groups. A Multivariate regression analysis suggested that RAS gene (p=0.039, HR=1.288,95%CI [1.072∼2.911]), metastatic organ number (p=0.033, HR=3.091,95%CI [1.090∼5.755]) and systemic therapy response (p=0.019, HR=0.622,95%CI [0.525∼0.811]) were independent prognostic factors in PTR population. Conclusion: We found that wild-type RAS gene was a favorable factor for the asymptomatic unresectable mCRC patients experiencing PTR.

Download Full-text

p53 and K-ras Gene Mutations Correlate With Tumor Aggressiveness But Are Not of Routine Prognostic Value in Colorectal Cancer

Journal of Clinical Oncology ◽

10.1200/jco.1999.17.5.1375 ◽

1999 ◽

Vol 17 (5) ◽

pp. 1375-1375 ◽

Cited By ~ 88

Author(s):

Silvia Tortola ◽

Eugenio Marcuello ◽

Isabel González ◽

Germán Reyes ◽

Rosa Arribas ◽

...

Keyword(s):

Colorectal Cancer ◽

Prognostic Significance ◽

Gene Mutations ◽

P53 Gene ◽

Radical Resection ◽

Genetic Alterations ◽

Rank Test ◽

P53 Mutations ◽

Ras Gene ◽

Ras Mutations

PURPOSE: p53 gene and K-ras mutations are among the most common genetic alterations present in colorectal cancer. The prognostic utility of such mutations remains controversial. The purpose of this study was to prospectively evaluate the prognostic significance of p53 and K-ras gene mutations in colorectal cancer. PATIENTS AND METHODS: One hundred forty patients were analyzed. Tumors belonging to the microsatellite mutator phenotype were excluded (n = 8). Mutations at the K-ras and p53 genes were detected and characterized by restriction fragment length polymorphism, single-strand conformation polymorphism, and sequencing, as appropriate. RESULTS: p53 mutations were detected in 66 (50%) and K-ras mutations were detected in 54 (41%) of the 132 patients. In 26 cases (20%), ras and p53 mutations coexisted; in 38 cases (29%), neither mutation was found. Multivariate analysis of the whole population analyzed (n = 132) showed that survival was strongly correlated with the presence of p53 mutations alone or in combination with K-ras mutations (P = .002; log-rank test). When only patients undergoing a radical resection were considered (R0; n = 101), p53 mutations were no longer of prognostic significance. CONCLUSION: p53 mutations alone or in combination with K-ras mutations are correlated with a worse outcome. However, the routine use of these mutations as prognostic markers in the clinical setting is not recommended.

Download Full-text