scholarly journals The prevalent KRAS exon 2 c.35 G>A mutation in metastatic colorectal cancer patients: A biomarker of worse prognosis and potential benefit of bevacizumab-containing intensive regimens?

2015 ◽  
Vol 93 (3) ◽  
pp. 190-202 ◽  
Author(s):  
Gemma Bruera ◽  
Katia Cannita ◽  
Alessandra Tessitore ◽  
Antonio Russo ◽  
Edoardo Alesse ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Potential Benefit ◽  
Exon 2 ◽  
Colorectal Cancer Patients ◽  
Kras Exon ◽  
Worse Prognosis

scholarly journals KRAS and NRAS mutational gene profile of metastatic colorectal cancer patients in Jordan: Molecular spectrum, frequency and distribution pattern

2019 ◽  
Author(s):  
Muhammad Awidi ◽  
Nidaa Ababneh ◽  
Maha Shomaf ◽  
Feras Al Fararjeh ◽  
Laila Owaidi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Distribution Pattern ◽  
Cancer Patients ◽  
Molecular Spectrum ◽  
Kras Mutations ◽  
Exon 2 ◽  
Ras Mutations ◽  
Colorectal Cancer Patients ◽  
Kras Exon

Abstract Background A constitutively active RAS protein in the absence of stimulation of the epidermal growth factor receptor (EGFR) is the result of mutations in KRAS and NRAS genes. Mutations in the KRAS exon 2 and outside exon 2 have been found to predict the resistance to anti-EGFR monoclonal therapy. A substantial proportion of metastatic colorectal cancer cases (mCRC) exhibit RAS mutations outside KRAS exon 2, particularly in KRAS exon 3 and 4 and NRAS exons 2, 3. No data about RAS mutations outside KRAS exon 2 are available for Jordanian patients with mCRC. We aim to study the molecular spectrum, frequency, and distribution pattern of KRAS and NRAS mutations in Jordanian patients with mCRC. Methods A cohort of 190 Jordanian metastatic colorectal cancer patients were enrolled in the trial. We detected mutations in exon 2 of the KRAS and NRAS gene as well as mutations outside of exon 2 using the StripAssay technique. The KRAS StripAssay covered 29 mutations and 22 NRAS mutations. Results Mutations were observed in 92 (48.42%) cases, and KRAS exon 2 accounted for 76 cases (83.69%). KRAS G12D was the most common mutation, occurring in 18 cases, followed by KRAS G12A in 16 cases, and G12T in 13 cases. Mutations outside of KRAS exon 2 represented 16.3% of the mutated cases. Among those, 6 cases (6.48%) carried mutations in NRAS exon 2, 3 and 10 cases (10.87%) in KRAS exon 3 and 4. Conclusion The frequency of NRAS and KRAS mutations outside of exon 2 appears to be higher in Jordanian patients in comparison with patients from western countries. KRAS mutations outside of exon 2 should be tested routinely to identify patients who should not be treated with anti-EGFR antibodies.

scholarly journals A phase 2 study of panitumumab with irinotecan as salvage therapy in chemorefractory KRAS exon 2 wild-type metastatic colorectal cancer patients

2019 ◽  
Vol 121 (5) ◽  
pp. 378-383 ◽  
Author(s):  
Elena Elez ◽  
Carles Pericay ◽  
Manuel Valladares-Ayerbes ◽  
Inmaculada Bando ◽  
Maria Jose Safont ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Salvage Therapy ◽  
Phase 2 ◽  
Wild Type ◽  
Exon 2 ◽  
Phase 2 Study ◽  
Colorectal Cancer Patients ◽  
Kras Exon

scholarly journals Influence of Postoperative Changes in Sarcopenia on Long-Term Survival in Non-Metastatic Colorectal Cancer Patients

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2410
Author(s):  
Chungyeop Lee ◽  
In-Ja Park ◽  
Kyung-Won Kim ◽  
Yongbin Shin ◽  
Seok-Byung Lim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Medical Center ◽  
The Body ◽  
Term Survival ◽  
Postoperative Changes ◽  
Asan Medical ◽  
Colorectal Cancer Patients

The effect of perioperative sarcopenic changes on prognosis remains unclear. We conducted a retrospective cohort study with 2333 non-metastatic colorectal cancer patients treated between January 2009 and December 2012 at the Asan Medical Center. The body composition at diagnosis was measured via abdominopelvic computed tomography (CT) using Asan-J software. Patients underwent CT scans preoperatively, as well as at 6 months–1 year and 2–3 years postoperatively. The primary outcome was the association between perioperative sarcopenic changes and survival. According to sarcopenic criteria, 1155 (49.5%), 890 (38.2%), and 893 (38.3%) patients had sarcopenia preoperatively, 6 months–1 year, and 2–3 years postoperatively, respectively. The 5-year overall survival (OS) (95.8% vs. 92.1%, hazard ratio (HR) = 2.234, p < 0.001) and 5-year recurrence-free survival (RFS) (93.2% vs. 86.2%, HR = 2.251, p < 0.001) rates were significantly lower in patients with preoperative sarcopenia. Both OS and RFS were lower in patients with persistent sarcopenia 2–3 years postoperatively than in those who recovered (OS: 96.2% vs. 90.2%, p = 0.001; RFS: 91.1% vs. 83.9%, p = 0.002). In multivariate analysis, postoperative sarcopenia was confirmed as an independent factor associated with decreased OS and RFS. Pre- and postoperative sarcopenia and changes in the condition during surveillance were associated with oncological outcomes.

scholarly journals Small EVs-Associated DNA as Complementary Biomarker to Circulating Tumor DNA in Plasma of Metastatic Colorectal Cancer Patients

2021 ◽  
Vol 14 (2) ◽  
pp. 128
Author(s):  
Silvia Galbiati ◽  
Francesco Damin ◽  
Dario Brambilla ◽  
Lucia Ferraro ◽  
Nadia Soriani ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Digital Pcr ◽  
Extracellular Vesicle ◽  
Circulating Tumor Dna ◽  
Mutation Status ◽  
Promising Practice ◽  
Colorectal Cancer Patients ◽  
Tumor Dna

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.

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