If you could look into the KRAS downstream signaling, it would be very valuable. Here is a brief summary in KRAS and lung cancer.

KRAS mutations occur in up to 30% of lung adenocarcinomas and are often mutually exclusive with other driver mutations in non-small cell lung cancer (NSCLC). There are a few aspects of lung cancer that could be addressed if we were aware of the KRAS mutation status of the tumor including (i) biology; (ii) classification and (iii) treatment.

(i) Biology:

A few studies have suggested that KRAS mutant lung tumors are more aggressive and carry a poor prognosis especially in advanced stages (1-5).

(ii) Classification:

In addition to EGFR and KRAS mutations, new driver mutations in NSCLC are gradually being identified including abnormalities in ALK, ROS, RET, HER2, BRAF, PIK3CA, AKT1, and MET among others. Considering the list of these mutations is growing and these driver mutations are often mutually exclusive, identifying the most prevalent abnormality (i.e., KRAS mutation) excludes the presence of others.

(iii) Treatment:

Considering the poor prognosis of KRAS mutant lung tumors, the effect of adjuvant platinum based chemotherapy on the outcome of this sub-type of NSCLC was examined (6). In this study, no benefit from providing adjuvant chemotherapy to KRAS mutant tumors was observed. Furthermore, it appeared that patients with codon 13 KRAS mutant tumors had shorter overall survival compared to wild type or codon 12 KRAS mutant tumors. Authors concluded that findings regarding codon 13 mutation requires further validation.

Currently, there is no approved therapy for treatment of KRAS mutant NSCLC however, multiple clinical trials are being conducted in this area.

In summary, although examining the mutation status of KRAS in NSCLC does not lead to a prominent clinical decision at this time, identifying KRAS genotype in NSCLC will help us exclude other sub-types and will help us direct patients to the appropriate clinical trials.

References.

1- http://www.ncbi.nlm.nih.gov/pubmed/23208128

2- http://www.ncbi.nlm.nih.gov/pubmed/23608713

3- http://www.ncbi.nlm.nih.gov/pubmed/10580029

4- http://www.ncbi.nlm.nih.gov/pubmed/23724098

5- http://www.ncbi.nlm.nih.gov/pubmed/2199829

6- http://www.ncbi.nlm.nih.gov/pubmed/23630215

Hi Sangeet

As you say there may be alot of bibliography about K-Ras mutation in cancer. Anyway I don`t know if it is already published or not , but apart of telling the percentage of ocurrence, It may be interesting to correlate each patients specific mutations with their prognosis or tumor characteristics such as aggresiveness, metastatic potential etc provided you have this data about the patients.

Hi, Ugutz, correlating tumor characteristics with KRAS mutation is very interesting. I will carry forward this idea and let you know.

Hello matthias, Yes I have the opportunity to chek other driver mutation. btw, thank you for the article. Do you have a full text copy of the same article? I do not have access to elsevier. it would be very helpful if you may send the article. Thank you for your suggestion.

If you could look into the KRAS downstream signaling, it would be very valuable. Here is a brief summary in KRAS and lung cancer.

KRAS mutations occur in up to 30% of lung adenocarcinomas and are often mutually exclusive with other driver mutations in non-small cell lung cancer (NSCLC). There are a few aspects of lung cancer that could be addressed if we were aware of the KRAS mutation status of the tumor including (i) biology; (ii) classification and (iii) treatment.

(i) Biology:

A few studies have suggested that KRAS mutant lung tumors are more aggressive and carry a poor prognosis especially in advanced stages (1-5).

(ii) Classification:

In addition to EGFR and KRAS mutations, new driver mutations in NSCLC are gradually being identified including abnormalities in ALK, ROS, RET, HER2, BRAF, PIK3CA, AKT1, and MET among others. Considering the list of these mutations is growing and these driver mutations are often mutually exclusive, identifying the most prevalent abnormality (i.e., KRAS mutation) excludes the presence of others.

(iii) Treatment:

Considering the poor prognosis of KRAS mutant lung tumors, the effect of adjuvant platinum based chemotherapy on the outcome of this sub-type of NSCLC was examined (6). In this study, no benefit from providing adjuvant chemotherapy to KRAS mutant tumors was observed. Furthermore, it appeared that patients with codon 13 KRAS mutant tumors had shorter overall survival compared to wild type or codon 12 KRAS mutant tumors. Authors concluded that findings regarding codon 13 mutation requires further validation.

Currently, there is no approved therapy for treatment of KRAS mutant NSCLC however, multiple clinical trials are being conducted in this area.

In summary, although examining the mutation status of KRAS in NSCLC does not lead to a prominent clinical decision at this time, identifying KRAS genotype in NSCLC will help us exclude other sub-types and will help us direct patients to the appropriate clinical trials.

References.

1- http://www.ncbi.nlm.nih.gov/pubmed/23208128

2- http://www.ncbi.nlm.nih.gov/pubmed/23608713

3- http://www.ncbi.nlm.nih.gov/pubmed/10580029

4- http://www.ncbi.nlm.nih.gov/pubmed/23724098

5- http://www.ncbi.nlm.nih.gov/pubmed/2199829

6- http://www.ncbi.nlm.nih.gov/pubmed/23630215

Hi Sangeet!

As previously mentioned by Fred (from L.A.), until now, MT-KRAS is not useful in the daily clinical practice as a predictive factor. As KRAS mutations (30% in NSCLC) are mutually exclusive with other driver mutations (e.g., EGFR, EML4-ALK, HER-2, among others), some groups do recommend to perform KRAS genotyping first, and to proceed with other studies in those pts with tumors habouring WT-KRAS.

Indeed, some targeted therapies (e.g., selumetinib, AZD6244, a MEK-inhibitor) are under clinical development in MT-KRAS tumors , with promising anti-tumor activity.

Hi Sangeet,

concerning studies mentioned by Gilberto Castro J., you can have a look at following llink:

http://www.ncbi.nlm.nih.gov/pubmed/23200175

You can get more than the percentage, as type of kras mutation , the relation with prognosis of NSCLC, and hopely in the near future will have some target to the kras.

Hi.

The K-RAS oncogene is another of the most commonly mutated oncogenes in lung cancer and is part of the EGFR signaling pathway. Most mutations in K-RAS occur in smokers, with 80%–90% occurring in codon 12 and G→T transversion. K-RAS mutations have not been found in SCLC. In lung adenocarcinoma, the K-RAS protein is mainly overexpressed, but the frequency of genetic alterations is greater in female smokers with lung cancer (26.2%) than in male smokers (17.4%), with an OR of 3.3. It has been found that adenocarcinomas in patients with K-RAS mutations and a history of smoking fail to benefit from adjuvant chemotherapy, and that the disease does not respond to EGFR inhibitors. There is also published evidence showing a higher frequency of “nonclassical” K-RAS mutations in women. However, these data need further validation and the role of these mutations in prognosis and therapy is still not accurately defined.

Reference. Lung cancer in women. Lung Cancer: Targets and Therapy 2012:3 79–89

Dear Sangeet,

Please give it a try to cBioPortal for Cancer Genomics to address your research question. From this portal, you should be able to combine primary data used in those papers cited by Fred Mortazavi and many other papers. The portal is really easy to use,- and by combining the data you should be able to come up with your own research hypothesis. Here is the link to the portal

http://www.cbioportal.org/public-portal/index.do

For example:

By using the The Cancer Genome Atlas data (532 samples-raw data NCI), case set: "All Tumors", and by entering the gene set: "KRAS", "EGFR"

You will find (under Mutual Exclusivity" tab) as Mortazavi stated- that there is no association between these:

"Odds Ratio: 1.591187 [no association]

95% Confidence Interval: 0.816603 - 3.100498

p-value: 0.119886 [Fisher's Exact Test"

There are many other tools for analyzing the data that is already out there.

A list of other analytical tools can be found here: https://tcga-data.nci.nih.gov/tcga/tcgaAnalyticalTools.jsp

Good luck!