Next-generation sequencing methodologies to detect low-frequency mutations: “Catch me if you can”

Menon, Vijay; Brash, Douglas E.

doi:10.1016/j.mrrev.2023.108471

Cited by 4 publications

(1 citation statement)

References 131 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The breakthrough in ultra-deep and sensitive metrics for mutation analysis in cancer patients has provided a modern approach to ctDNA analysis that focuses on variant allele frequency (VAF) [51]. However, in the literature, VAF is often substituted by mutant allele frequency (MAF), which carries the same meaning.…”

Section: Variant Allele Frequency (Vaf)mentioning

confidence: 99%

Variant Allele Frequency Analysis of Circulating Tumor DNA as a Promising Tool in Assessing the Effectiveness of Treatment in Non-Small Cell Lung Carcinoma Patients

Galant,

Nicoś,

Kuźnar-Kamińska

et al. 2024

Cancers

View full text Add to dashboard Cite

Despite the different possible paths of treatment, lung cancer remains one of the leading causes of death in oncological patients. New tools guiding the therapeutic process are under scientific investigation, and one of the promising indicators of the effectiveness of therapy in patients with NSCLC is variant allele frequency (VAF) analysis. VAF is a metric characterized as the measurement of the specific variant allele proportion within a genomic locus, and it can be determined using methods based on NGS or PCR. It can be assessed using not only tissue samples but also ctDNA (circulating tumor DNA) isolated from liquid biopsy. The non-invasive characteristic of liquid biopsy enables a more frequent collection of material and increases the potential of VAF analysis in monitoring therapy. Several studies have been performed on patients with NSCLC to evaluate the possibility of VAF usage. The research carried out so far demonstrates that the evaluation of VAF dynamics may be useful in monitoring tumor progression, remission, and recurrence during or after treatment. Moreover, the use of VAF analysis appears to be beneficial in making treatment decisions. However, several issues require better understanding and standardization before VAF testing can be implemented in clinical practice. In this review, we discuss the difficulties in the application of ctDNA VAF analysis in clinical routine, discussing the diagnostic and methodological challenges in VAF measurement in liquid biopsy. We highlight the possible applications of VAF-based measurements that are under consideration in clinical trials in the monitoring of personalized treatments for patients with NSCLC.

show abstract

Section: Variant Allele Frequency (Vaf)mentioning

confidence: 99%

Variant Allele Frequency Analysis of Circulating Tumor DNA as a Promising Tool in Assessing the Effectiveness of Treatment in Non-Small Cell Lung Carcinoma Patients

Galant,

Nicoś,

Kuźnar-Kamińska

et al. 2024

Cancers

View full text Add to dashboard Cite

show abstract

Methods and applications of genome-wide profiling of DNA damage and rare mutations

Pfeifer,

Jin

2024

Nat Rev Genet

View full text Add to dashboard Cite

Genetic evolution of keratinocytes to cutaneous squamous cell carcinoma

Tandukar,

Deivendran,

Chen

et al. 2024

Preprint

View full text Add to dashboard Cite

We performed multi-omic profiling of epidermal keratinocytes, precancerous actinic keratoses, and squamous cell carcinomas to understand the molecular transitions during skin carcinogenesis. Single-cell mutational analyses showed that most keratinocytes in normal skin had lower mutation burdens than melanocytes and fibroblasts, however keratinocytes with TP53 or NOTCH1 mutations had substantially higher mutation burdens, suggesting that these mutations prime keratinocytes for transformation by increasing their mutation rate. Mutational profiling and spatial transcriptomics on squamous cell carcinomas adjacent to actinic keratoses revealed TERT promoter and CDKN2A mutations emerging in actinic keratoses, whereas additional mutations inactivating ARID2 and activating the MAPK-pathway delineated the transition to squamous cell carcinomas. Spatial variation in gene expression patterns was common in both tumor and immune cells, with high expression of checkpoint molecules at the invasive front of tumors. In conclusion, this study documents key events during the evolution of cutaneous squamous cell carcinoma.

show abstract

Next-generation sequencing methodologies to detect low-frequency mutations: “Catch me if you can”

Cited by 4 publications

References 131 publications

Variant Allele Frequency Analysis of Circulating Tumor DNA as a Promising Tool in Assessing the Effectiveness of Treatment in Non-Small Cell Lung Carcinoma Patients

Variant Allele Frequency Analysis of Circulating Tumor DNA as a Promising Tool in Assessing the Effectiveness of Treatment in Non-Small Cell Lung Carcinoma Patients

Methods and applications of genome-wide profiling of DNA damage and rare mutations

Genetic evolution of keratinocytes to cutaneous squamous cell carcinoma

Contact Info

Product

Resources

About