A Highly Verified Assay for KRAS Mutation Detection in Tissue and Plasma of Lung, Colorectal, and Pancreatic Cancer

Li, Jing; Gan, Stephanie D.; Blair, A; Min, Kyungji; Rehage, Taraneh; Hoeppner, Corey; Halait, H.; Brophy, Victoria H.

doi:10.5858/arpa.2017-0471-oa

Cited by 7 publications

(4 citation statements)

References 15 publications

(13 reference statements)

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“…Moreover, the test involves many washing and incubation steps with a total analysis time of about 2 h [ 48 ]. Compared to the previously reported biosensors for ctDNA detection in real samples ( Table S3 ) [ 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 ], the advantages of the proposed multi-plex test are related mostly to the cost, run time, and simplicity, as well as the universality and advanced multiplexing potential.…”

Section: Discussionmentioning

confidence: 95%

Rapid Multiplex Strip Test for the Detection of Circulating Tumor DNA Mutations for Liquid Biopsy Applications

et al. 2022

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In the era of personalized medicine, molecular profiling of patient tumors has become the standard practice, especially for patients with advanced disease. Activating point mutations of the KRAS proto-oncogene are clinically relevant for many types of cancer, including colorectal cancer (CRC). While several approaches have been developed for tumor genotyping, liquid biopsy has been gaining much attention in the clinical setting. Analysis of circulating tumor DNA for genetic alterations has been challenging, and many methodologies with both advantages and disadvantages have been developed. We here developed a gold nanoparticle-based rapid strip test that has been applied for the first time for the multiplex detection of KRAS mutations in circulating tumor DNA (ctDNA) of CRC patients. The method involved ctDNA isolation, PCR-amplification of the KRAS gene, multiplex primer extension (PEXT) reaction, and detection with a multiplex strip test. We have optimized the efficiency and specificity of the multiplex strip test in synthetic DNA targets, in colorectal cancer cell lines, in tissue samples, and in blood-derived ctDNA from patients with advanced colorectal cancer. The proposed strip test achieved rapid and easy multiplex detection (normal allele and three major single-point mutations) of the clinically relevant KRAS mutations in ctDNA in blood samples of CRC patients with high specificity and repeatability. This multiplex strip test represents a minimally invasive, rapid, low-cost, and promising diagnostic tool for the detection of clinically relevant mutations in cancer patients.

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Section: Discussionmentioning

confidence: 95%

Rapid Multiplex Strip Test for the Detection of Circulating Tumor DNA Mutations for Liquid Biopsy Applications

et al. 2022

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“…In one recent study, authors found that only 42.8% of patients with EOPC expressed a KRAS mutation [10]. The common types of KRAS are on exon 2 codons 12 and 13 with relative frequency of 71-80% [35,36] and mostly located at G12C, G12D and G12R in pancreatic cancer [37,38]. There is no data on frequency in EOPC verses LOPC.…”

Section: Kirsten Rat Sarcoma Virus (Kras) Mutationmentioning

confidence: 99%

Early-onset pancreatic cancer: a review of molecular mechanisms, management, and survival

et al. 2022

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Objectives: Early-onset pancreatic cancer (EOPC) -defined as pancreatic cancer diagnosed before the age of 50 years -is associated with a poor prognosis as compared to later-onset pancreatic cancer (LOPC). Emerging evidence suggests that EOPC may exhibit a genetic signature and tumor biology that is distinct from that of LOPC. We review genetic mutations that are more prevalent in EOPC relative to LOPC and discuss the potential impact of these mutations on treatment and survival.Materials and Methods: Using PubMed and Medline, the following terms were searched and relevant citations assessed: "early onset pancreatic cancer," "late onset pancreatic cancer," "pancreatic cancer," "pancreatic cancer genes," and "pancreatic cancer targeted therapy."Results: Mutations in CDKN2, FOXC2, and SMAD4 are significantly more common in EOPC as compared to LOPC. In addition, limited data suggest that PI3KCA mutations are more frequently observed in EOPC as compared to LOPC. KRAS mutations are relatively rare in EOPC.Conclusions: Genetic mutations associated with EOPC are distinct from those of LOPC. The preponderance of the evidence suggest that poor outcomes in EOPC are related both to advanced stage of presentation and unique tumor biology. The molecular and genetic features of EOPC warrant further investigation in order to optimize management.

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“…Mutations located in codons 12 and 13 are multiallelic, but the changes c.35G>A and c.38G>A (p.Gly12Asp and p.Gly13Asp, respectively) are the most common [11]. Additionally, the frequency of these mutations varies between populations in CRC patients, with an overall frequency of 33%-50% [12][13][14]. Besides the molecular variability in the KRAS gene, CRC also has a versatile clinical presentation.…”

Section: Introductionmentioning

confidence: 99%

KRAS Exon 2 Mutations in Patients with Sporadic Colorectal Cancer: Prevalence Variations in Mexican and Latin American Populations

Venegas-Rodríguez,

Hernández-Sandoval,

Gutiérrez-Angulo

et al. 2024

Cancers

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We searched for the prevalence of actionable somatic mutations in exon 2 of the KRAS gene in western Mexican patients with CRC. Tumor tissue DNA samples from 150 patients with sporadic CRC recruited at the Civil Hospital of Guadalajara were analyzed. Mutations in exon 2 of the KRAS gene were identified using Sanger sequencing, and the data were analyzed considering clinical–pathological characteristics. Variants in codon 12 (rs121913529 G>A, G>C, and G>T) and codon 13 (rs112445441 G>A) were detected in 26 patients (with a prevalence of 17%). No significant associations were found between these variants and clinical–pathological characteristics (p > 0.05). Furthermore, a comprehensive search was carried out in PubMed/NCBI and Google for the prevalence of KRAS exon 2 mutations in Latin American populations. The 17 studies included 12,604 CRC patients, with an overall prevalence of 30% (95% CI = 0.26–0.35), although the prevalence ranged from 13 to 43% across the different data sources. Determining the variation and frequency of KRAS alleles in CRC patients will enhance their potential to receive targeted treatments and contribute to the understanding of the genomic profile of CRC.

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A Highly Verified Assay for KRAS Mutation Detection in Tissue and Plasma of Lung, Colorectal, and Pancreatic Cancer

Cited by 7 publications

References 15 publications

Rapid Multiplex Strip Test for the Detection of Circulating Tumor DNA Mutations for Liquid Biopsy Applications

Rapid Multiplex Strip Test for the Detection of Circulating Tumor DNA Mutations for Liquid Biopsy Applications

Early-onset pancreatic cancer: a review of molecular mechanisms, management, and survival

KRAS Exon 2 Mutations in Patients with Sporadic Colorectal Cancer: Prevalence Variations in Mexican and Latin American Populations

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