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Analysis of Chromothripsis by Combined FISH and Microarray Analysis.

Ruth N MacKinnon1,2

  • 1Department of Medicine (St. Vincent's), University of Melbourne, Melbourne, VIC, Australia. ruth.mackinnon@svha.org.au.

Methods in Molecular Biology (Clifton, N.J.)
|March 23, 2018
PubMed
Summary

Fluorescence in situ hybridization (FISH) combined with genomic data analysis helps unravel complex chromosome rearrangements. This approach clarifies genome organization and low-frequency abnormalities, crucial for cancer research.

Keywords:
ChromosomeChromothripsisCytogeneticsCytogenomicsM-BANDM-FISHMetaphase FISHMicroarraySNP array

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Area of Science:

  • Genomics
  • Cytogenetics
  • Molecular Biology

Background:

  • DNA microarrays identify copy number changes but lack information on chromosome organization and balanced rearrangements.
  • Complex genome rearrangements, such as those from chromothripsis, require detailed structural analysis.
  • Understanding chromosome abnormalities in cancer necessitates identifying clonal populations and specific structural changes.

Purpose of the Study:

  • To describe strategies for determining the organization of highly rearranged genomes.
  • To integrate SNP array data with Fluorescence in situ hybridization (FISH) methods.
  • To address uncertainties in whole genome or mate-pair sequencing data regarding complex rearrangements.

Main Methods:

  • Utilizing metaphase Fluorescence in situ hybridization (FISH) on intact metaphase chromosomes.
  • Combining SNP array data with various FISH techniques.
  • Applying FISH as a single-cell technique to identify low-frequency and clonal chromosome abnormalities.

Main Results:

  • FISH provides crucial information on the organization of abnormal chromosomes, including balanced rearrangements and centromere abnormalities.
  • The combined approach successfully elucidates the structure of highly rearranged genomes.
  • FISH can distinguish chromosome abnormalities within the same or different clonal populations.

Conclusions:

  • Strategic use of metaphase FISH, integrated with SNP array data, is essential for detailed genome organization analysis.
  • This combined methodology overcomes limitations of DNA microarrays and sequencing in characterizing complex rearrangements.
  • The approach is vital for understanding cancer genomics and resolving complex structural variations.