scholarly journals Specify Other KRAS Codon 61 Mutation

2020 ◽  
Author(s):  
Keyword(s):  
Kras Codon ◽  
Codon 61

scholarly journals Pyrosequencing analysis of KRAS codon 61 mutations in Thai patients with advanced colorectal cancer

2015 ◽  
Vol 9 (1) ◽  
Author(s):  
Chinachote Teerapakpinyo ◽  
Phanni Wanthong ◽  
Mathawee Aumchaaumchaya ◽  
Piyamai Chankate ◽  
Warisa Kaikeaw ◽  
...  
Keyword(s):  
Advanced Colorectal Cancer ◽  
Growth Factor Receptor ◽  
Egfr Signaling ◽  
Small G Protein ◽  
Epidermal Growth ◽  
Low Prevalence ◽  
Kras Codon ◽  
Pyrosequencing Method ◽  
Pyrosequencing Analysis ◽  
Codon 61

AbstractBackground, coding for a small G-protein downstream of epidermal growth factor receptor (EGFR) plays an important role in the EGFR signaling network. Mutation inObjectivesTo develop an in-house pyrosequencing method to screen forMaterials and MethodsDNA extracted from FFPE specimens was screened forResultsOf the 74 samples with undetectable codon 12/13 mutation examined, two (2.7%) were found to harbor mutation in codon 61.ConclusionDespite the low prevalence of

Analysis of gene mutations in KRAS, NRAS, BRAF, and PIK3CA in patients who received systemic chemotherapy with metastatic gastric cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 27-27
Author(s):  
Masaru Fukahori
Keyword(s):  
Gastric Cancer ◽  
Poor Prognosis ◽  
Systemic Chemotherapy ◽  
Gene Mutations ◽  
Metastatic Gastric Cancer ◽  
Braf V600e ◽  
Mutation Status ◽  
Exon 9 ◽  
Kras Codon ◽  
Codon 61

27 Background: Previous studies showed that gene mutations of KRAS, NRAS, BRAF, and PIK3CA are associated with a poor prognosis or resistance of anti-EGFR antibody in metastatic colorectal cancer. On the other hand, the frequency and clinical significance of these gene mutations have not been clarified in metastatic gastric cancer (mGC). Methods: We gathered formalin-fixed paraffin-embedded tumor samples from 168 patients who were diagnosed gastric cancer and underwent gastrectomy between September 1995 and March 2008. Among 168 patients, we selected the mGC patients who received systemic chemotherapy. We retrospectively evaluated the mutation status of KRAS (exon2, 3, 4), NRAS (exon 2, 3), BRAF (exon 15) and PIK3CA (exon 9, 20) and prognosis in patients who received chemotherapy by gene mutation status. Results: A total 125 of patients were included in this analysis. Regimens of first line chemotherapy were 5-FU (24.0%), CPT-11/CDDP (31.2%), S-1 (33.6%), 5-FU/MTX (8.0%) and others (3.2%). Mutations of KRAS codon 12/13 (6.4%), PIK3CA exon9 (4%), PIK3CA exon20 (0.8%), and NRAS codon 12/13 (2.4%) were detected by direct-sequence method. Mutations of KRAS codon 61, KRAS codon 146, BRAF V600E and NRAS codon 61 were not detected. There were no significant differences in overall survival (OS) by mutation status of KRAS and PIK3CA. Patients with NRAS codon 12/13 mutation had poor prognosis (MSTF15.5 vs 9.4 months, adjusted HR: 5.327(95%CI: 1.566-18.096)). Conclusions: Mutations in KRAS codon 61, KRAS codon 146, BRAF V600E, NRAS codon 61 were not detected, and frequency of mutation in PIK3CA exon 9, PIK3CA exon 20 and NRAS codon 61 were rare in mGC. Although our study has several limitations, mutation in NRAS codon 12/13 may be a poor prognostic factor in mGC who received systemic chemotherapy and further accumulation of cases are needed.

Mutations in NRAS codon 61, KRAS codon 146, and BRAF V600E as prognostic factors in patients who received anti-EGFR antibody for metastatic colorectal cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14126-e14126
Author(s):  
Naoki Takahashi ◽  
Yasuhide Yamada ◽  
Hirokazu Taniguchi ◽  
Kohei Akiyoshi ◽  
Yoshitaka Honma ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Poor Prognosis ◽  
Tumor Response ◽  
Progression Free Survival ◽  
Braf V600e ◽  
Antibody Treatment ◽  
Kras Codon ◽  
Egfr Antibody ◽  
Codon 61

e14126 Background: Previous studies showed that gene mutations (NRAS, BRAF, PIK3CA) are associated with a poor prognosis or resistance of anti-EGFR antibody in metastatic colorectal cancer (mCRC) patients with wild type (WT) of KRAS codon 12/13 (KRAS-WT). However the significance of these biomarkers has not been clarified. In addition, EGFR immunohistochemistry (IHC) and EGFR gene amplification to evaluate the efficacy of anti-EGFR antibody treatment has not been reported for mCRC. Methods: We evaluated tumor response and survival in patients who received anti-EGFR antibody by mutation analysis of KRAS, NRAS, BRAF, and PIK3CA in KRAS-WT patients with mCRC. Tumor DNA samples are obtained from patients treated in our hospital with anti-EGFR antibody between August 2008 and August 2011. Results: A total of 117 patients were enrolled in this analysis, including 100 KRAS-WT patients. Seventy-one patients (60.7%) were all WT for KRAS, NRAS, BRAF, and PIK3CA, and 46 patients (39.3%) had at least 1 mutation or had insufficient DNA samples to analyze. Mutations of KRAS codon 61 (2 patients), KRAS codon 146 (5), BRAF V600E (2), PIK3CA exon9 (8), NRAS codon 12/13 (2), and NRAS codon 61 (5) were detected. No patients had a mutation of PIK3CA exon 20. Patients with at least 1 mutation had no response. Mutations of NRAS codon 61, KRAS codon 146, and BRAF V600E were associated with a shorter progression free survival (PFS) compared with all WT patients (p=0.049, p=0.004, p=0.036, respectively). Twelve patients (12% of KRAS-WT patients) with a mutation of NRAS codon 61, KRAS codon146, and BRAF V600E had poor prognosis compared with the other KRAS-WT patients (PFS, 6.4 vs 2.0 months, p<0.001; overall survival (OS), 13.7 vs 7.9 months, p=0.012). In all WT patients, moderate to strong EGFR IHC was associated with a better response rate than negative and weak IHC (p=0.046). Conclusions: Mutations of NRAS codon 61, KRAS codon 146, and BRAF V600E could be a strong prognostic factor of anti-EGFR antibody in patients with mCRC. Combination of IHC and DISH of EGFR could identify patients with a tumor response to anti-EGFR antibody in patients that are all WT for KRAS, NRAS, BRAF, and PIK3CA.

COLD-PCR protocols to enrich KRAS codon 61 and 146 mutations in heterogeneous tumor samples.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. e22125-e22125
Author(s):  
Davide Nicoli ◽  
Federica Torricelli ◽  
Enrico Farnetti ◽  
Adriana Albini ◽  
Bruno Casali
Keyword(s):  
Kras Codon ◽  
Heterogeneous Tumor ◽  
Codon 61

RAS status in circulating-tumor DNA (ctDNA) and outcomes during rechallenge treatments with anti-EGFR antibodies in metastatic colorectal cancer (mCRC).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 166-166
Author(s):  
Yu Sunakawa ◽  
Masato Nakamura ◽  
Masahiro Ishizaki ◽  
Masato Kataoka ◽  
Hironaga Satake ◽  
...  
Keyword(s):  
Circulating Tumor Dna ◽  
Line Treatment ◽  
Phase Ii Trials ◽  
Ras Status ◽  
Post Hoc ◽  
Kras Codon ◽  
Tumor Dna ◽  
Clinical Trial Information ◽  
Egfr Antibody ◽  
Codon 61

166 Background: We have evaluated rechallenge treatment with irinotecan plus cetuximab (JACCRO CC-08, n = 36) or panitumumab (JACCRO CC-09, n = 25) in patients (pts) with KRAS wild-type mCRC [Tsuji A, WCGC 2018], and the primary endpoint of PFS rate at 3 months was met in both trials. RAS status in ctDNA may potentially predict responders of the rechallenge treatment in mCRC resistant to anti-EGFR antibody [Cremolini C, JAMA Oncol 2018]. Methods: A post-hoc biomarker study was performed to investigate an association between RAS status in ctDNA and clinical outcomes in the JACCRO phase II trials comprised mCRC pts who achieved a clinical benefit from 1st-line anti-EGFR antibody-based therapy, then had a disease progression at 2nd-line treatment. RAS status in ctDNA was analyzed at the time points of baseline, 8 weeks, and progression using OncoBEAM RAS CRC Kit for specific KRAS/ NRAS mutations, using cut-off value defined as the number of beads with amplified-mutant molecules specifically set per each codon. Results: Sixteen pts (median 67.5-y old, 50% of PS0, 25% of right-sided primary, cet/pani: 4/12) were enrolled in this study, with response rate of 0% and disease control rate (DCR) of 62.5%. RAS mutations (mt) were found at the baseline in 6 out of 16 pts (all left-sided pts with KRAS codon 12, codon 61 and/or NRAS codon 61 mt simultaneously). Pts without RAS mt at baseline experienced longer PFS in 1st-line treatment (11.5 vs. 9.0 m). The DCR was 33% in pts with RAS mt in ctDNA, while it was 80% in pts without RAS mt at baseline. Pts with RAS mt at baseline had significantly shorter PFS and OS than pts without RAS mt [median PFS 2.3 vs 4.7 m, HR 6.2 (95%CI 1.6-30.5), p = 0.013; median OS 3.8 vs. 16.0 m, HR 12.4 (95%CI 2.7-87.7), p = 0.0028]. Six of 10 pts without RAS mt at baseline acquired RAS mt ( KRAS/ NRAS codon 12 or 61) in ctDNA at progression, however there was no difference in survival between pts with/without RAS mt at progression. Conclusions: Our study demonstrated that RAS status in ctDNA using OncoBEAM RAS CRC Kit predicts survival of rechallenge treatment with anti-EGFR antibody in mCRC pts. These data can support the application of RAS monitoring into clinical practice. Clinical trial information: UMIN000015914/UMIN000015916.

Use of KRAS codon 13 mutations to predict response to neoadjuvant chemoradiation therapy in patients with rectal adenocarcinoma.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 453-453
Author(s):  
Marjun Philip Duldulao ◽  
Wendy Lee ◽  
Zhenbin Chen ◽  
Wenyan Li ◽  
Rebecca A. Nelson ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Kras Mutation ◽  
Pathologic Complete Response ◽  
Neoadjuvant Chemoradiation ◽  
Chemoradiation Therapy ◽  
Wild Type ◽  
Kras Mutations ◽  
Neoadjuvant Chemoradiation Therapy ◽  
Kras Codon ◽  
Codon 61

453 Background: The predictive role of KRAS mutation in therapeutic management of metastatic colorectal cancer has been much investigated. However, the association between KRAS mutations and rectal cancer response to neoadjuvant chemoradiation therapy (CRT) remains unclear. Our objectives were to determine the incidence of KRAS mutations in patients with rectal cancer and identify potential correlations with response to CRT. Methods: Patients with Stage II-III rectal cancer (n=148) from a multicenter prospective clinical trial were assessed. DNA was extracted from pretreatment tumor biopsies; and genotyping of KRAS was completed by PCR and direct sequencing. All patients underwent pre-operative CRT followed by surgery; and treatment response was evaluated by a pathologist. Surgical specimens without evidence of residual disease were deemed to have a pathologic complete response (pCR). Results: Overall, 60 of 148 (40.5%) patients had KRAS mutation. Breakdown of the different KRAS mutations revealed that 40 (66.7%) mutations occurred in codon 12, 12 (20.0%) in codon 13, 5 (8.3%) in codon 61, and 3 (5.0%) in other locations. When examining the relationship between KRAS and CRT response, we observed that detection of any KRAS mutation was associated with a decreased rate of pCR compared to wild-type KRAS (13.3% vs. 33.0%, respectively; p=0.007). More specifically, patients with KRAS codon 13 mutations did not respond to CRT compared to non-codon 13 mutations (p=0.037). In contrast, the detection of codon 12 or codon 61 mutations was not associated with response to CRT ( Table ). Conclusions: Patients with KRAS mutation have lower response rates to CRT compared to patients with wild-type KRAS. However, our results indicate that this association does not apply to all KRAS mutations, rather to KRAS codon 13 mutation alone. Thus, these data are the first to show that patients with KRAS codon 13 mutations may not derive pCR from neoadjuvant CRT. [Table: see text]

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