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 ◽  
...  
2016 ◽  
Vol 33 (7) ◽  
Author(s):  
Zhe-Zhen Li ◽  
Long Bai ◽  
Feng Wang ◽  
Zi-Chen Zhang ◽  
Fang Wang ◽  
...  

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14164-e14164
Author(s):  
Dan Rhodes ◽  
Sean Eddy ◽  
Paul Williams ◽  
Mark Tomilo ◽  
Seth Sadis ◽  
...  

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.


2021 ◽  
Vol 14 (2) ◽  
pp. 128
Author(s):  
Silvia Galbiati ◽  
Francesco Damin ◽  
Dario Brambilla ◽  
Lucia Ferraro ◽  
Nadia Soriani ◽  
...  

It is widely accepted that assessing circular tumor DNA (ctDNA) in the plasma of cancer patients is a promising practice to evaluate somatic mutations from solid tumors noninvasively. Recently, it was reported that isolation of extracellular vesicles improves the detection of mutant DNA from plasma in metastatic patients; however, no consensus on the presence of dsDNA in exosomes has been reached yet. We analyzed small extracellular vesicle (sEV)-associated DNA of eleven metastatic colorectal cancer (mCRC) patients and compared the results obtained by microarray and droplet digital PCR (ddPCR) to those reported on the ctDNA fraction. We detected the same mutations found in tissue biopsies and ctDNA in all samples but, unexpectedly, in one sample, we found a KRAS mutation that was not identified either in ctDNA or tissue biopsy. Furthermore, to assess the exact location of sEV-associated DNA (outside or inside the vesicle), we treated with DNase I sEVs isolated with three different methodologies. We found that the DNA inside the vesicles is only a small fraction of that surrounding the vesicles. Its amount seems to correlate with the total amount of circulating tumor DNA. The results obtained in our experimental setting suggest that integrating ctDNA and sEV-associated DNA in mCRC patient management could provide a complete real-time assessment of the cancer mutation status.


2018 ◽  
Vol 57 (12) ◽  
pp. 1727-1729
Author(s):  
Anne Gulbech Ording ◽  
Buket Öztürk ◽  
Karen-Lise Garm Spindler ◽  
Henrik Toft Sørensen ◽  
Margaret McCusker ◽  
...  

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