A clinical algorithm for efficient, high-resolution cytogenomic analysis of uncultured perinatal tissue samples

作者：Morgen Eric K; Maire Georges; Kolomietz Elena^*

来源：European Journal of Medical Genetics, 2012, 55(8-9): 446-454.

DOI：10.1016/j.ejmg.2012.04.005

• Oligonucleotide array comparative genomic hybridization Quantitative fluorescence polymerase chain reaction
• Products of conception
• Gestational trophoblastic disease
• Molecular diagnosis

Purpose: Cytogenetic analysis of solid tissue is indispensable in perinatal care, reproductive planning, and detection of gestational trophoblastic disease. Unfortunately, methods in common use suffer from drawbacks including culture artifact, low resolution, and high cost. We propose a new diagnostic algorithm based on direct genetic analysis of tissues (without cell culture) using QF-PCR and array CGH.
Methods: Study samples consisted of specimens submitted to the cytogenetics laboratory between January and June of 2011 that were split and analyzed in parallel by our traditional algorithm (culture and G-banding, plus an interphase FISH aneuploidy panel for culture failures) and the proposed "no-culture" algorithm (first line QF-PCR, plus array CGH on normal QF-PCRs). Data on clinical impact, cost, and turnaround time were collected.
Results: Forty specimens were included. The algorithms produced results that were fully concordant in 22 cases, partially concordant in 9 cases, and discordant in 9 cases. The no-culture algorithm detected new, clinically-significant abnormalities in 8 of 40 cases (20%), corrected the sex chromosome assortment in 1 case, reduced the analysis failure rate from 10% to 0%, and provided at least one of these three important benefits in 12 of 40 cases (30%). The algorithm also demonstrated a reduced cost per-specimen and per diagnosis, as well as improved turnaround time, with virtually all cases reported per guidelines.
Conclusion: These striking results favor the "no-culture" algorithm, which may have the potential to replace standard cytogenetic methods in the clinical laboratory.

• 出版日期2012-9