Comparison of KRAS mutation status between primary tumor and metastasis in Chinese colorectal cancer patients

2016 ◽  
Vol 33 (7) ◽  
Author(s):  
Zhe-Zhen Li ◽  
Long Bai ◽  
Feng Wang ◽  
Zi-Chen Zhang ◽  
Fang Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Primary Tumor ◽  
Kras Mutation ◽  
Mutation Status ◽  
Colorectal Cancer Patients ◽  
Kras Mutation Status

Genetic analysis of KRAS mutation status in metastatic colorectal cancer patients

Neoplasma ◽  
2009 ◽  
Vol 56 (3) ◽  
pp. 275-278 ◽  
Author(s):  
K. Zavodna ◽  
M. Konecny ◽  
T. Krivulcik ◽  
S. Spanik ◽  
R. Behulova ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Genetic Analysis ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Kras Mutation ◽  
Mutation Status ◽  
Colorectal Cancer Patients ◽  
Kras Mutation Status

A qPCR gene expression module test to predict resistance to cetuximab in colorectal cancers independent of KRAS mutation status.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14164-e14164
Author(s):  
Dan Rhodes ◽  
Sean Eddy ◽  
Paul Williams ◽  
Mark Tomilo ◽  
Seth Sadis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Cancer Patients ◽  
Microarray Data ◽  
Kras Mutation ◽  
Mutation Status ◽  
Module Test ◽  
Colorectal Cancer Patients ◽  
Expression Module ◽  
Kras Mutation Status

e14164 Background: While KRAS mutation predicts resistance to anti-EGFR therapy in colorectal cancer, not all KRAS wild-type patients benefit from such therapy, suggesting that complementary biomarkers capable of identifying additional non-responsive patients would have clinical utility. Methods: To search for such a biomarker, we studied the relationship of cetuximab response with twelve gene expression modules, derived from an unsupervised analysis of 20 independent microarray datasets comprising more than 2,000 colorectal cancer patients. Each module represents a set of highly co-expressed genes related to an important aspect of colorectal cancer variability. Two cetuximab-treated cohorts were studied. The first was a Phase II clinical trial (Khambata-Ford et al, J Clin Oncol, 2007) with accompanying microarray data from pre-treatment biopsies. The second was a single-institution study of cetuximab response from which formalin-fixed paraffin-embedded primary tumor specimens were available. Results: In the first study, module scores were computed by averaging co-expressed module genes in the microarray data. In the second study, module scores were generated from a qPCR gene expression module test, OncoScore Colon, which quantifies modules by averaging three representative module genes relative to housekeeping controls. Notably, in both studies, the mesenchymal module was significantly associated with cetuximab resistance, with module positive patients tending to progress on cetuximab within 10 weeks. Additionally, the status of this module was independent of KRAS mutation status—KRAS mutations occurred in both module-positive and -negative patients. Future clinical studies will continue to test the predictive capacity of the module in regards to cetuximab resistance and other mechanisms. Conclusions: In summary, this study demonstrates the value of a gene expression module-based qPCR panel for stratifying colorectal cancer patients for treatment response, and suggests that our approach may have immediate utility for cetuximab treatment response prediction.

scholarly journals Discordance of KRAS Mutational Status between Primary Tumors and Liver Metastases in Colorectal Cancer: Impact on Long-Term Survival Following Radical Resection

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2148
Author(s):  
Francesco Ardito ◽  
Francesco Razionale ◽  
Lisa Salvatore ◽  
Tonia Cenci ◽  
Maria Vellone ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Primary Tumor ◽  
Kras Mutation ◽  
Colorectal Tumor ◽  
Term Survival ◽  
Primary Tumors ◽  
Mutation Status ◽  
Primary Colorectal Tumor ◽  
Kras Mutation Status

If KRAS mutation status of primary colorectal tumor is representative of corresponding colorectal liver metastases (CRLM) mutational pattern, is controversial. Several studies have reported different rates of KRAS discordance, ranging from 4 to 32%. Aim of this study is to assess the incidence of discordance and its impact on overall survival (OS) in a homogenous group of patients. KRAS mutation status was evaluated in 107 patients resected for both primary colorectal tumor and corresponding CRLM at the same institution, between 2007 and 2018. Discordance rate was 15.9%. Its incidence varied according to the time interval between the two mutation analyses (p = 0.025; Pearson correlation = 0.2) and it was significantly higher during the first 6 months from the time of primary tumor evaluation. On multivariable analysis, type of discordance (wild-type in primary tumor, mutation in CRLM) was the strongest predictor of poor OS (p < 0.001). At multivariable logistic regression analysis, the number of CRLM >3 was an independent risk factor for the risk of KRAS discordance associated with the worst prognosis (OR = 4.600; p = 0.047). Results of our study suggested that, in the era of precision medicine, possibility of KRAS discordance should be taken into account within multidisciplinary management of patients with metastatic colorectal cancer.

Awareness of KRAS testing by oncologists and panitumumab use in colorectal cancer patients: A European survey.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 547-547
Author(s):  
Jorg Trojan ◽  
Aliki Taylor ◽  
Jan-Henrik Terwey ◽  
Gerry Downey ◽  
George Kafatos ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Kras Mutation ◽  
Wild Type ◽  
Nras Mutation ◽  
Mutation Status ◽  
Kras Status ◽  
Level Of Knowledge ◽  
High Level ◽  
Colorectal Cancer Patients ◽  
Kras Mutation Status

547 Background: Panitumumab (Pmab) is licensed for treatment in metastatic colorectal cancer (mCRC) patients with wild type KRAS mutation status (US) and wild type RAS (KRAS and NRAS) mutation status (most other countries). To resolve uncertainties about KRAS testing, a survey and medical records review (MRR) are being carried out in Europe in three rounds: the first two rounds (2012-2013) evaluated KRAS testing and round 3 is evaluating RAS testing. These studies are specific obligations in Europe for the conditional marketing authorization for Pmab. Here we present results of rounds 1 and 2. Methods: Eligible oncologists were contacted by telephone in nine European countries (France, Germany, Italy, Spain, Czech Republic, Netherlands, Belgium, Denmark, and Sweden). To be eligible, the physician was required to be a practicing oncologist and have prescribed Pmab to mCRC patients. Results: 299 of 301 (99.3%) oncologists participating in the survey were aware of the need to perform KRAS testing prior to first dose of Pmab and 294 (97.7%) were aware of patients’ KRAS mutation status prior to first dose. 283 of 301 (94.0%) did not prescribe Pmab to mCRC patients with mutant or unknown KRAS status. 164 physicians administered Pmab simultaneously with oxaliplatin-containing chemotherapy to patients and 10 (6.1%) to patients with mutant or unknown KRAS status. 306 patients from 79 participating oncologists were included in the MRR. 302 of 306 mCRC patients (98.7%) were tested for KRAS tumor status, known by the oncologist before first dose of Pmab. 299 of 302 patients (99.0%) had wild-type KRAS tumor status. 83 of 85 patients (97.6%) treated with Pmab and oxaliplatin-containing chemotherapy had wild-type KRAS tumor status. 55 of 56 linked pathology laboratories (98.2%) participated in a Quality Assurance scheme; all used a CE marked or otherwise validated KRAS detection method. Conclusions: Results from both studies show a high level of knowledge among oncologists of the need for KRAS testing in mCRC patients prior to treatment with Pmab and the contraindication with oxaliplatin-containing chemotherapy with mutant or unknown KRAS tumour status. The final round of this study evaluating RAS testing in Europe is currently underway.

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