title: Formalin-fixed paraffin-embedded clinical tissues show spurious copy number changes in array-CGH profiles.
abstract: Formalin-fixed paraffin-embedded (FFPE) archival clinical specimens are invaluable in discovery of prognostic and therapeutic targets for diseases such as cancer. However, the suitability of FFPE-derived genetic material for array-based comparative genomic hybridization (array-CGH) studies is underexplored. In this study, genetic profiles of matched FFPE and fresh-frozen specimens were examined to investigate DNA integrity differences between these sample types and determine the impact this may have on genetic profiles. Genomic DNA was extracted from three patient-matched FFPE and fresh-frozen clinical tissue samples. T47D breast cancer control cells were also grown in culture and processed to yield a fresh T47D sample, a fresh-frozen T47D sample and a FFPE T47D sample. DNA was extracted from all the samples; array-CGH conducted and genetic profiles of matched samples were then compared. A loss of high molecular weight DNA was observed in the FFPE clinical tissues and FFPE T47D samples. A dramatic increase in absolute number of genetic alterations was observed in all FFPE tissues relative to matched fresh-frozen counterparts. In future, alternative fixation and tissue-processing procedures, and/or new DNA extraction and CGH profiling protocols, may be implemented, enabling identification of changes involved in disease progression using stored clinical specimens.
authors.affiliation: UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin, Ireland.
authors.forename: E A
authors.initials: EA
authors.lastname: Mc Sherry
authors.forename: A
authors.initials: A
authors.lastname: Mc Goldrick
authors.forename: E W
authors.initials: EW
authors.lastname: Kay
authors.forename: A M
authors.initials: AM
authors.lastname: Hopkins
authors.forename: W M
authors.initials: WM
authors.lastname: Gallagher
authors.forename: P A
authors.initials: PA
authors.lastname: Dervan
mesh_terms: D002869:Chromosome Aberrations; D005189:False Positive Reactions; D005557:Formaldehyde / Q000494:pharmacology*; D018628:Gene Dosage; D006801:Humans; D009693:Nucleic Acid Hybridization / Q000379:methods; D016612:Paraffin Embedding / Q000379:methods*; D011786:Quality Control; D046888:Tissue Array Analysis / Q000379:methods*; D014021:Tissue Preservation / Q000379:methods; D014407:Tumor Cells, Cultured
chemical_list: D005557:Formaldehyde