Document Type

Article

Publication Date

11-1-2007

Keywords

Chromosome Aberrations, False Positive Reactions, Formaldehyde, Gene Dosage, Humans, Nucleic Acid Hybridization, Paraffin Embedding, Quality Control, Tissue Array Analysis, Tissue Preservation, Tumor Cells, Cultured

Comments

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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.

Disciplines

Medical Pathology | Pathology

Citation

McSherry EA, McGoldrick A, Kay EW, Hopkins AM, Gallagher WM, Dervan PA. Formalin-Fixed Paraffin-Embedded Clinical Tissues Show Spurious Copy Number Changes in Array-CGH Profiles. Clinical Genetics. 2007;72(5):441-7.

PubMed ID

17935507

DOI Link

10.1111/j.1399-0004.2007.00882.x