scholarly journals Genetic Heterogeneity in Colorectal Cancer and its Clinical Implications

2015 ◽  
Vol 28 (3) ◽  
pp. 370 ◽  
Author(s):  
Rui Barranha ◽  
José Luís Costa ◽  
Fátima Carneiro ◽  
José Carlos Machado
Keyword(s):  
Colorectal Cancer ◽  
Next Generation Sequencing ◽  
Genetic Heterogeneity ◽  
Targeted Therapies ◽  
Poor Prognosis ◽  
Genetic Diagnosis ◽  
Influence Factors ◽  
Clinical Implications ◽  
Generation Sequencing ◽  
Colorectal Tumours

<p>Despite the recent advances in the development of complementary diagnostic exams and modern targeted therapies, colorectal cancer remains a major cause of morbidity and mortality worldwide. In this context, a lot of research has been conducted in the last years to find new markers of poor prognosis. The existence of a complex tumour architecture formed by multiple subclones genetically heterogeneous has been increasingly considered in recent studies as an element of particular importance. This feature seems to influence factors as relevant as the representativeness of tumour biopsies for genetic diagnosis and the efficacy of targeted therapies.<br />There is growing evidence suggesting a relation between genetic heterogeneity and the patients’ prognosis. The widespread use of next-generation sequencing techniques will allow a better understanding of the true degree of genetic heterogeneity in colorectal tumours, its causes and impact on the course of the disease. In this review we intend to analyse the recent findings related to the genetic heterogeneity of colorectal cancer, as well as its major clinical implications.</p>

scholarly journals Colorectal Cancer Biomarkers in the Era of Personalized Medicine

2019 ◽  
Vol 9 (1) ◽  
pp. 3 ◽  
Author(s):  
Jai Patel ◽  
Mei Fong ◽  
Megan Jagosky
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Therapy Response ◽  
Dose Intensity ◽  
Cancer Biomarkers ◽  
Clinical Implications ◽  
Test Results ◽  
First Line ◽  
Genomic Markers ◽  
Generation Sequencing

The 5-year survival probability for patients with metastatic colorectal cancer has not drastically changed over the last several years, nor has the backbone chemotherapy in first-line disease. Nevertheless, newer targeted therapies and immunotherapies have been approved primarily in the refractory setting, which appears to benefit a small proportion of patients. Until recently, rat sarcoma (RAS) mutations remained the only genomic biomarker to assist with therapy selection in metastatic colorectal cancer. Next generation sequencing has unveiled many more potentially powerful predictive genomic markers of therapy response. Importantly, there are also clinical and physiologic predictive or prognostic biomarkers, such as tumor sidedness. Variations in germline pharmacogenomic biomarkers have demonstrated usefulness in determining response or risk of toxicity, which can be critical in defining dose intensity. This review outlines such biomarkers and summarizes their clinical implications on the treatment of colorectal cancer. It is critical that clinicians understand which biomarkers are clinically validated for use in practice and how to act on such test results.

Next-generation sequencing for guiding matched targeted therapies in people with relapsed or metastatic cancer

2021 ◽  
Vol 2021 (10) ◽  
Author(s):  
Farasat Kazmi ◽  
Nipun Shrestha ◽  
Stephen Booth ◽  
David Dodwell ◽  
Francesca Aroldi ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Targeted Therapies ◽  
Metastatic Cancer ◽  
Next Generation ◽  
Generation Sequencing

Rapid Somatic Mutation Testing in Colorectal Cancer by Use of a Fully Automated System and Single-Use Cartridge: A Comparison with Next-Generation Sequencing

2018 ◽  
Vol 3 (2) ◽  
pp. 178-184 ◽  
Author(s):  
M Rabie Al-Turkmani ◽  
Kelley N Godwin ◽  
Jason D Peterson ◽  
Gregory J Tsongalis
Keyword(s):  
Colorectal Cancer ◽  
Next Generation Sequencing ◽  
Ffpe Tissue ◽  
Braf V600e ◽  
Automated System ◽  
Next Generation ◽  
Tissue Samples ◽  
Tissue Sections ◽  
Single Use ◽  
Generation Sequencing

AbstractBackgroundMolecular tests have been increasingly used in the management of various cancers as more targeted therapies are becoming available as treatment options. The Idylla™ system is a fully integrated, cartridge-based platform that provides automated sample processing (deparaffinization, tissue digestion, and DNA extraction) and real-time PCR-based mutation detection with all reagents included in a single-use cartridge. This retrospective study aimed at evaluating both the Idylla KRAS and NRAS-BRAF-EGFR492 Mutation Assay cartridges (research use only) against next-generation sequencing (NGS) by using colorectal cancer (CRC) tissue samples.MethodsForty-four archived formalin-fixed paraffin-embedded (FFPE) CRC tissue samples previously analyzed by targeted NGS were tested on the Idylla system. Among these samples, 17 had a mutation in KRAS proto-oncogene, GTPase (KRAS), 5 in NRAS proto-oncogene, GTPase (NRAS), and 12 in B-Raf proto-oncogene, serine/threonine kinase (BRAF) as determined using the Ion AmpliSeq 50-gene Cancer Hotspot Panel v2. The remaining 10 samples were wild-type for KRAS, NRAS, and BRAF. Two 10-μm FFPE tissue sections were used for each Idylla run, 1 for the KRAS cartridge, and 1 for the NRAS-BRAF-EGFR492 cartridge. All cases met the Idylla minimum tumor content requirement for KRAS, NRAS, and BRAF (≥10%). Assay reproducibility was evaluated by testing commercial controls derived from human cell lines, which had an allelic frequency of 50% and were run in triplicate.ResultsThe Idylla system successfully detected all mutations previously identified by NGS in KRAS (G12C, G12D, G12V, G13D, Q61K, Q61R, A146T), NRAS (G12V, G13R, Q61H), and BRAF (V600E). Compared with NGS, Idylla had a sensitivity of 100%. Analysis of the mutated commercial controls demonstrated agreement with the expected result for all samples and 100% reproducibility. The Idylla system produced results quickly with a turnaround time of approximately 2 h.ConclusionThe Idylla system offers reliable and sensitive testing of clinically actionable mutations in KRAS, NRAS, and BRAF directly from FFPE tissue sections.

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