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Chromosome Replicating Timing Combined with Fluorescent In situ Hybridization
Published on: December 10, 2012
Rearranged During Transfection Rearrangement Detection by Fluorescence In Situ Hybridization Compared With Other
Anne Mc Leer1,2,3, Julie Mondet1,2,3, Nelly Magnat2
1Université Grenoble Alpes, Grenoble, France.
Introduction:
RET rearrangements occur in 1% to 2% NSCLCs. Since no clinically validated RET antibody is currently available, fluorescence in situ hybridization (FISH) is often used as a screening tool to identify patients likely to benefit from RET-targeted therapy. In this study, we performed a comprehensive review of publications in which RET-rearrangement testing was performed by FISH and compared the methods and results with our data.
Methods:
The findings of an electronic search for publications using RET-FISH in lung cancer were compared with the results obtained at the Grenoble University Hospital where 784 EGFR -, KRAS -, ALK-, and ROS1-negative NSCLCs were tested by RET break-apart FISH and confirmed by RNA-sequencing (RNA-seq).
Results:
Out of the 85 publications using RET-FISH analysis, 52 pertained to patients with lung cancer. The most often used positivity threshold was 15%. Six publications compared RET-FISH with at least one other molecular technique on at least eight samples, and the concordance was variable, from 5.9% to 66.7% for FISH-positive cases. Regarding our data, out of the 784 analyzed samples, 32 (4%) were positive by RET-FISH. The concordance between RET-FISH and RNA-seq in RET-FISH positive samples was 69%.
Conclusions:
Overall, both existing literature and our data suggest that RET-FISH testing can be used for rapid screening of RET rearrangements in NSCLC. Nevertheless, using an orthogonal technique such as RNA-seq to confirm RET-FISH-positive cases is essential for ensuring that only patients likely to benefit from RET-target therapy receive the treatment.
Insights
RET rearrangements are screened using fluorescence in situ hybridization (FISH) in non-small cell lung cancer (NSCLC). While FISH is a useful screening tool, RNA-sequencing confirmation is crucial for accurate patient selection for RET-targeted therapy.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genetics
Background:
- RET rearrangements occur in 1-2% of non-small cell lung cancers (NSCLCs).
- No clinically validated RET antibody is available, making fluorescence in situ hybridization (FISH) a common screening method.
- Accurate identification of RET rearrangements is critical for guiding RET-targeted therapy.
Purpose of the Study:
- To review and compare existing literature on RET-FISH testing with in-house data.
- To evaluate the efficacy and concordance of RET-FISH for identifying RET rearrangements in NSCLC.
- To assess the necessity of orthogonal confirmation for RET-FISH positive cases.
Main Methods:
- A comprehensive literature review of studies using RET-FISH for rearrangement testing was performed.
- Data from Grenoble University Hospital, including 784 EGFR-, KRAS-, ALK-, and ROS1-negative NSCLCs tested by RET break-apart FISH, were analyzed.
- RNA-sequencing (RNA-seq) was used to confirm RET-FISH results.
Main Results:
- Out of 85 publications, 52 focused on lung cancer, with 15% being the most common positivity threshold for RET-FISH.
- Concordance between RET-FISH and other molecular techniques varied widely (5.9% to 66.7%) in published studies.
- In-house data showed 4% (32/784) of NSCLC samples were RET-FISH positive, with a 69% concordance between RET-FISH and RNA-seq.
Conclusions:
- RET-FISH serves as a valuable tool for rapid screening of RET rearrangements in NSCLC.
- Orthogonal confirmation using techniques like RNA-seq is essential to ensure accurate patient selection for RET-targeted therapies.
- Combining RET-FISH screening with RNA-seq confirmation optimizes patient stratification for targeted treatment.
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