1. Copy number analysis by low coverage whole genome sequencing using ultra low-input DNA from formalin-fixed paraffin embedded tumor tissue.
- Author
-
Kader T, Goode DL, Wong SQ, Connaughton J, Rowley SM, Devereux L, Byrne D, Fox SB, Mir Arnau G, Tothill RW, Campbell IG, and Gorringe KL
- Subjects
- Breast Neoplasms pathology, Carcinoma, Merkel Cell pathology, Cell Line, Tumor, Cohort Studies, Cost-Benefit Analysis, DNA Copy Number Variations, DNA Repair, Female, Gene Library, Genome, Human, Genomics methods, High-Throughput Nucleotide Sequencing, Humans, Oligonucleotide Array Sequence Analysis, Paraffin chemistry, Polymorphism, Single Nucleotide, Prognosis, Sequence Analysis, DNA, DNA analysis, Formaldehyde chemistry, Gene Dosage
- Abstract
Unlocking clinically translatable genomic information, including copy number alterations (CNA), from formalin-fixed paraffin-embedded (FFPE) tissue is challenging due to low yields and degraded DNA. We describe a robust, cost-effective low-coverage whole genome sequencing (LC WGS) method for CNA detection using 5 ng of FFPE-derived DNA. CN profiles using 100 ng or 5 ng input DNA were highly concordant and comparable with molecular inversion probe (MIP) array profiles. LC WGS improved CN profiles of samples that performed poorly using MIP arrays. Our technique enables identification of driver and prognostic CNAs in archival patient samples previously deemed unsuitable for genomic analysis due to DNA limitations.
- Published
- 2016
- Full Text
- View/download PDF