AI Article Synopsis
- Osimertinib, a third-generation TKI aimed at treating lung cancer, faces challenges like drug resistance due to genetic amplifications, with FISH being the standard test for detection but limited by subjectivity.
- A study analyzed 317 NSCLC tissue samples using next-generation sequencing (NGS), comparing results with FISH from 96 samples, leading to a model achieving 74% agreement with FISH that excels in identifying amplifications, especially when gene copy numbers are 5 or higher.
- The research also uncovered common mutations in NSCLC patients resistant to osimertinib, highlighting mechanisms of resistance such as gene amplifications and specific mutations, suggesting NGS offers a detailed insight into genetic changes amid treatment resistance.
Article Abstract
Purposes: Osimertinib, one of the third-generation -tyrosine kinase inhibitors (TKIs) designed to target T790M mutation, significantly improves the prognosis of lung cancer. However, drug resistance still happens and amplification is responsible for one of the main causes. Fluorescence hybridization (FISH) is the gold standard for amplification detection, but fundamentally limited by observer subjectivity. Herein, we assessed the value of next-generation sequencing (NGS) method in amplification detection in non-small cell lung cancer (NSCLC), as well as revealed the mutation profiling of NSCLC patients with osimertinib resistance to provide some valuable clues to the mechanisms of resistance.
Methods: A total of 317 cancer tissue samples from 317 NSCLC patients at time of progression following osimertinib were submitted to NGS and only 96 tissues were tested by FISH simultaneously. With FISH results as gold standard, enumeration algorithm was applied to establish the optimal model for identifying amplification using gene copy number (GCN) data.
Results: The optimal model for identifying amplification was constructed based on the GCN of , , and , which achieved a 74.0% overall agreement with FISH and performed well in identifying amplification except polysomy with a sensitivity of 85.7% and a specificity of 93.9%. The inconsistency between NGS and FISH occurred mainly in polysomy subtype, while GCN ≥ 5 could be reliably recognized by NGS. Moreover, the most frequently mutated genes in NSCLC patients with osimertinib resistance were (59.94%), followed by (43.85%), (9.46%), (6.31%), and ATM (5.36%). The known resistance mechanisms, including amplification, (C797S, L718Q/R), , , , , , , and mutations were also disclosed in our cohort.
Conclusions: NGS assay can achieve a high concordance with FISH in amplification detection and has advantages in portraying various genetic alterations, which is of worthy in clinical promotion.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532092 | PMC |
| http://dx.doi.org/10.3389/fonc.2024.1470827 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Unveiling the role of sintering temperatures in the physical properties of Cu-Mg ferrite nanoparticles for photocatalytic application.
Heliyon
December 2024
Department of Physics, University of Dhaka, Dhaka, 1000, Bangladesh.
This research presents an explicit analysis of the effects of sintering temperature (T) on the structural, morphological, magnetic, and optical properties of CuMgFeO nanoferrites synthesized via the sol-gel method. To accomplish it, Cu-Mg ferrite NPs were sintered at temperatures ranging from 300 to 800 °C in increments of 100 with a constant holding duration of 5 h. Thermogravimetric analysis was used to observe the degradation of organic components and the thermally stable zone of the material.
View Article and Find Full Text PDFMultiple Instance Learning for WSI: A comparative analysis of attention-based approaches.
J Pathol Inform
December 2024
Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, Lisbon 1049-001, Portugal.
Whole slide images (WSI), obtained by high-resolution digital scanning of microscope slides at multiple scales, are the cornerstone of modern Digital Pathology. However, they represent a particular challenge to artificial intelligence (AI)-based/AI-mediated analysis because pathology labeling is typically done at slide-level, instead of tile-level. It is not just that medical diagnostics is recorded at the specimen level, the detection of oncogene mutation is also experimentally obtained, and recorded by initiatives like The Cancer Genome Atlas (TCGA), at the slide level.
View Article and Find Full Text PDFStructural profile and diversity of immunoglobulin genes in the Arctic Fox.
Vet J
December 2024
College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China. Electronic address:
Immunoglobulins are important components of humoral immunity and play a crucial role in protecting the body from external antigens. The Arctic fox is an important member of furbearer farming, but due to the lack of research on the immune system of the Arctic fox, animal welfare regarding Arctic fox farming has still not received enough attention. In this study, we used the Arctic fox as a research subject, described the gene locus structure of the Arctic fox immunoglobulin germline by genome comparison, and analysed the mechanism of expression diversity of the antibody pool of the Arctic fox by rapid amplification of cDNA 5' ends and high-throughput sequencing.
View Article and Find Full Text PDFCRISPR technology combined with isothermal amplification methods for the diagnosis of Candida albicans infection.
Clin Chim Acta
December 2024
Department of Clinical Laboratory, the First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China; Department of Clinical Laboratory, Anhui Public Health Clinical Center, Hefei, People's Republic of China. Electronic address:
Since Candida albicans, a type of fungus, causes severe infections that pose a significant threat to human health, its rapid detection is critical in clinical antifungal therapy. Traditional fungal diagnostic approaches are largely based on the culture method. This method is time-consuming and laborious, taking about 48-72 h, and cannot identify emerging species, making it unsuitable for critically ill patients with bloodstream infections, sepsis, and so on.
View Article and Find Full Text PDFAttenuated sex-related DNA methylation differences in cancer highlight the magnitude bias mediating existing disparities.
Biol Sex Differ
December 2024
State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, China.
Background: DNA methylation (DNAm) influences both sex differences and cancer development, yet the mechanisms connecting these factors remain unclear.
Methods: Utilizing data from The Cancer Genome Atlas, we conducted a comprehensive analysis of sex-related DNAm effects in nine non-reproductive cancers, compared to paired normal adjacent tissues (NATs), and validated the results using independent datasets. First, we assessed the extent of sex differential DNAm between cancers and NATs to explore how sex-related DNAm differences change in cancerous tissues.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!