Related Experiment Video
Updated: Mar 30, 2026
09:45
Mosaic Zebrafish Transgenesis for Functional Genomic Analysis of Candidate Cooperative Genes in Tumor Pathogenesis
Published on: March 31, 2015
11.9K
Clinical Implications of Variant ALK FISH Rearrangement Patterns
Xin Gao1, Lynette M Sholl, Mizuki Nishino
1*Brigham and Women's Hospital, Boston, Massachusetts; and †Dana-Farber Cancer Institute, Boston, Massachusetts.
Summary
Anaplastic lymphoma kinase (ALK) rearrangement patterns in non-small-cell lung cancer (NSCLC) impact treatment response. Five-prime (5’) deletion on FISH may indicate false positives, suggesting confirmatory testing is beneficial.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genetics
Background:
- Break-apart fluorescence in situ hybridization (FISH) is FDA-approved for detecting anaplastic lymphoma kinase (ALK) rearrangements in non-small-cell lung cancer (NSCLC).
- Identifying ALK rearrangements is crucial for patient selection for ALK kinase inhibitor therapy.
- FISH assay interpretation can be challenging, with different rearrangement patterns potentially having clinical significance.
Purpose of the Study:
- To investigate potential clinical differences based on specific anaplastic lymphoma kinase (ALK) rearrangement patterns detected by fluorescence in situ hybridization (FISH).
- To evaluate the correlation between different FISH rearrangement patterns and clinical characteristics, immunohistochemistry (IHC), next-generation sequencing (NGS), and response to crizotinib in NSCLC patients.
Main Methods:
- A retrospective review of 1614 NSCLC patients with ALK testing was conducted.
- Clinical data, including response to crizotinib, were analyzed for patients with ALK rearrangement by FISH.
- Immunohistochemistry (IHC) and targeted next-generation sequencing (NGS) were performed when available for correlative analysis.
Main Results:
- Of 1614 patients, 82 (5.1%) had ALK rearrangement by FISH, categorized into split signals (30), 5' deletion (25), or unavailable (27).
- Patients with 5' deletion were older and had more extensive smoking histories compared to other groups.
- While all split signal cases were IHC positive, 3/21 (14%) 5' deletion cases were IHC negative. Patients with 5' deletion showed a smaller tumor response magnitude to crizotinib (p=0.03).
Conclusions:
- The 5' deletion pattern on ALK FISH may represent a subset of non-small-cell lung cancer (NSCLC) cases that are not true ALK rearrangements.
- These findings suggest that some 5' deletion cases might be false positives, potentially impacting treatment decisions.
- Corroborative testing using IHC or NGS is recommended for cases with 5' deletion on ALK FISH to confirm rearrangement status.
Related Concept Videos
02:32Exon Recombination
4.3K
The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes.
Exon shuffling follows “splice frame rules.” Each exon...
Exon shuffling follows “splice frame rules.” Each exon...
4.3K
02:18Alternative RNA Splicing
26.3K
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
26.3K
02:02Cis-regulatory Sequences
12.2K
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
12.2K
02:26Comparing Copy Number Variations and SNPs
19.3K
Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
19.3K
01:25Genetic Variation
1.6K
Genetic variation is the diversity in DNA sequences found among individuals of the same species. This diversity is crucial for a species' survival because it helps organisms adapt to environmental changes. Genetic variation begins with fertilization, where an egg and sperm cell merge. Each of these cells carries 23 chromosomes, up to 46 in the fertilized egg. Chromosomes are long DNA strands that contain genes, the basic units of heredity.
Genes exist in different versions called alleles,...
Genes exist in different versions called alleles,...
1.6K
02:53Conservative Site-specific Recombination and Phase Variation
7.3K
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
7.3K