scholarly journals Patterns of germline and somatic mutations in 16 mismatch repair associated genes analyzed with next generation sequencing (NGS) in colorectal cancer with EMAST (+) and/or MSI-high

2018 ◽  
Vol 29 ◽  
pp. viii179
Author(s):  
S.-C. Chang ◽  
P.-C. Lin ◽  
C.-C. Lin ◽  
J.-K. Lin ◽  
Y.-T. Lan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Next Generation Sequencing ◽  
Mismatch Repair ◽  
Somatic Mutations ◽  
Next Generation ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

scholarly journals Less frequently mutated genes in colorectal cancer: evidences from next-generation sequencing of 653 routine cases

2016 ◽  
Vol 69 (9) ◽  
pp. 767-771 ◽  
Author(s):  
Umberto Malapelle ◽  
Pasquale Pisapia ◽  
Roberta Sgariglia ◽  
Elena Vigliar ◽  
Maria Biglietto ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Next Generation Sequencing ◽  
Somatic Mutations ◽  
Gene Mutations ◽  
Next Generation ◽  
Genomic Landscape ◽  
Next Generation Sequencing Ngs ◽  
Pcr Targeting ◽  
Diagnostic Setting ◽  
Generation Sequencing

AimsThe incidence of RAS/RAF/PI3KA and TP53 gene mutations in colorectal cancer (CRC) is well established. Less information, however, is available on other components of the CRC genomic landscape, which are potential CRC prognostic/predictive markers.MethodsFollowing a previous validation study, ion-semiconductor next-generation sequencing (NGS) was employed to process 653 routine CRC samples by a multiplex PCR targeting 91 hotspot regions in 22 CRC significant genes.ResultsA total of 796 somatic mutations in 499 (76.4%) tumours were detected. Besides RAS/RAF/PI3KA and TP53, other 12 genes showed at least one mutation including FBXW7 (6%), PTEN (2.8%), SMAD4 (2.1%), EGFR (1.2%), CTNNB1 (1.1%), AKT1 (0.9%), STK11 (0.8%), ERBB2 (0.6%), ERBB4 (0.6%), ALK (0.2%), MAP2K1 (0.2%) and NOTCH1 (0.2%).ConclusionsIn a routine diagnostic setting, NGS had the potential to generate robust and comprehensive genetic information also including less frequently mutated genes potentially relevant for prognostic assessments or for actionable treatments.

Using mutational load in next generation sequencing (NGS) to identify mismatch repair (MMR) deficiency in colorectal cancer (CRC).

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 3565-3565
Author(s):  
Francesca Battaglin ◽  
Zsofia Kinga Stadler ◽  
Andrea Cercek ◽  
Rona D. Yaeger ◽  
Neil Howard Segal ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Next Generation Sequencing ◽  
Mismatch Repair ◽  
Mutational Load ◽  
Next Generation ◽  
Mmr Deficiency ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

scholarly journals Comparison of KRAS mutation analysis of colorectal cancer samples by standard testing and next-generation sequencing

2014 ◽  
Vol 67 (9) ◽  
pp. 764-767 ◽  
Author(s):  
Nishi Kothari ◽  
Michael J Schell ◽  
Jamie K Teer ◽  
Timothy Yeatman ◽  
David Shibata ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Next Generation Sequencing ◽  
Clinical Laboratory ◽  
Clinical Care ◽  
Next Generation ◽  
Illumina Platform ◽  
Kras Mutations ◽  
Standard Testing ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

AimsBased on KRAS testing, the subset of patients with metastatic colorectal cancer (CRC) that could benefit from anti-EGFR therapy can be better delineated. Though KRAS testing has become significantly more prevalent over the last few years, methods for testing remain heterogeneous and discordance has been reported between methods.MethodsIn this study, we examined a CRC patient population and compared KRAS testing done in Clinical Laboratory Improvement Amendments (CLIA) approved laboratories as part of standard clinical care and by next-generation sequencing (NGS) using the Illumina platform. Discordances were further evaluated with manual review of the NGS testing.ResultsOut of 468 CRC patient samples, 77 had KRAS testing done by both CLIA assay and NGS. There were concordant results between testing methodologies in 74 out of 77 patients, or 96% (95% CI 89% to 99%). There were three patient samples that showed discordant results between the two methods of testing. Upon further investigation of the NGS results for the three discordant cases, one sample showed a low level of the mutation seen in the standard testing, one sample showed low tumour fraction and a third did not show any evidence of the mutation that was found with the standard assay. Five patients had KRAS mutations not typically tested with standard testing.ConclusionsOverall there was a high concordance rate between NGS and standard testing for KRAS. However, NGS revealed mutations that are not tested for with standard KRAS assays that might have clinical impact with regards to the role for anti-EGFR therapy.

scholarly journals Carrier molecules and extraction of circulating tumor DNA for next generation sequencing in colorectal cancer

2016 ◽  
Vol 59 (2) ◽  
pp. 54-58 ◽  
Author(s):  
Martin Beránek ◽  
Igor Sirák ◽  
Milan Vošmik ◽  
Jiří Petera ◽  
Monika Drastíková ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Next Generation Sequencing ◽  
Somatic Mutations ◽  
Circulating Tumor Dna ◽  
Next Generation ◽  
Sequencing Data ◽  
Polyadenylic Acid ◽  
Sperm Dna ◽  
Tumor Dna ◽  
Generation Sequencing

The aims of the study were:i) to compare circulating tumor DNA (ctDNA) yields obtained by different manual extraction procedures,ii) to evaluate the addition of various carrier molecules into the plasma to improve ctDNA extraction recovery, andiii) to use next generation sequencing (NGS) technology to analyzeKRAS,BRAF, andNRASsomatic mutations in ctDNA from patients with metastatic colorectal cancer. Venous blood was obtained from patients who suffered from metastatic colorectal carcinoma. For plasma ctDNA extraction, the following carriers were tested: carrier RNA, polyadenylic acid, glycogen, linear acrylamide, yeast tRNA, salmon sperm DNA, and herring sperm DNA. Each extract was characterized by quantitative real-time PCR and next generation sequencing. The addition of polyadenylic acid had a significant positive effect on the amount of ctDNA eluted. The sequencing data revealed five cases of ctDNA mutated inKRASand one patient with aBRAFmutation. An agreement of 86% was found between tumor tissues and ctDNA. Testing somatic mutations in ctDNA seems to be a promising tool to monitor dynamically changing genotypes of tumor cells circulating in the body. The optimized process of ctDNA extraction should help to obtain more reliable sequencing data in patients with metastatic colorectal cancer.

Homologous Recombination Deficiency Alterations in Colorectal Cancer: Clinical, Molecular, and Prognostic Implications

2021 ◽  
Author(s):  
Roberto Moretto ◽  
Andrew Elliott ◽  
Jian Zhang ◽  
Hiroyuki Arai ◽  
Marco Maria Germani ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Next Generation Sequencing ◽  
Homologous Recombination ◽  
Mismatch Repair ◽  
Immune Cell ◽  
Statistical Tests ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Next Generation ◽  
Generation Sequencing

Abstract Background Tumors with homologous recombination (HR) deficiency (HRD) show high sensitivity to platinum salts and PARP-inhibitors in several malignancies. In colorectal cancer (CRC), the role of HRD alterations is mostly unknown. Methods Next generation sequencing, whole transcriptome sequencing and whole exome sequencing were conducted using CRC samples submitted to a commercial Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Tumors with pathogenic/presumed pathogenic mutations in 33 genes involved in the HR pathway were considered HRD, the others HR proficient (HRP). Furthermore, tumor samples from patients enrolled in the phase III TRIBE2 study comparing upfront FOLFOXIRI/bevacizumab versus FOLFOX/bevacizumab were analyzed with next generation sequencing. The analyses were separately conducted in microsatellite stable/proficient mismatch repair (MSS/pMMR) and microsatellite instable-high/deficient mismatch repair (MSI-H/dMMR) groups. All statistical tests were 2-sided. Results Of 9321 CRC tumors, 1270 (13.6%) and 8051 (86.4%) were HRD and HRP, respectively. HRD tumors were more frequent among MSI-H/dMMR than MSS/pMMR tumors (73.4% vs 9.5%, p and q < 0.001). In MSS/pMMR group, HRD tumors were more frequently tumor mutational burden high (8.1% vs 2.2% P and q < 0.001) and PD-L1 positive (5.0% vs 2.4%, P and q = 0.001), enriched in all immune cell and fibroblast populations, and genomic loss of heterozygosity-high (16.2% vs 9.5%, P = .03). In the TRIBE2 study, patients with MSS/pMMR and HRD tumors (10.7%) showed longer overall survival compared to MSS/pMMR and HRP ones (40.2 vs 23.8 months; hazard ratio = 0.66; 95% confidence interval = 0.45–0.98, P = .04). Consistent results were reported in the multivariable model (hazard ratio = 0.67; 95% confidence ratio = 0.45–1.02, P = .07). No interaction effect was evident between HR groups and treatment arm. Conclusions HRD tumors are a distinctive subgroup of MSS/pMMR CRCs with specific molecular and prognostic characteristics. The potential efficacy of agents targeting the HR system and immune check-point inhibitors in this subgroup is worth of clinical investigation.

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