Design and validation of an oligonucleotide microarray for the detection of genomic rearrangements associated with common hereditary cancer syndromes
| Autor: | Debora Mancini-DiNardo, Adam Murray, Matthew Ryder, Jeremy Schoenberger, Collin Burton, Nick Woolstenhulme, Christopher Arnell, Jayson Holladay, Natalia Gutin, Kelsey Moyes, Jonathan Craft, Thaddeus Judkins, Benjamin B. Roa, Aaron Theisen |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
Microarray Hereditary breast and ovarian cancer Biology MLH1 Translocation Genetic symbols.namesake MUTYH Neoplastic Syndromes Hereditary Genetic screening medicine Humans Genetic testing Oligonucleotide Array Sequence Analysis Genetics Sanger sequencing medicine.diagnostic_test Microarray analysis techniques Research Reproducibility of Results Microarray analysis Exons Genomics medicine.disease Lynch syndrome MutS Homolog 2 Protein Oncology Large genomic rearrangements Mutation symbols Comparative genomic hybridization |
| Zdroj: | Journal of Experimental & Clinical Cancer Research : CR |
| ISSN: | 1756-9966 |
| Popis: | Background Conventional Sanger sequencing reliably detects the majority of genetic mutations associated with hereditary cancers, such as single-base changes and small insertions or deletions. However, detection of genomic rearrangements, such as large deletions and duplications, requires special technologies. Microarray analysis has been successfully used to detect large rearrangements (LRs) in genetic disorders. Methods We designed and validated a high-density oligonucleotide microarray for the detection of gene-level genomic rearrangements associated with hereditary breast and ovarian cancer (HBOC), Lynch, and polyposis syndromes. The microarray consisted of probes corresponding to the exons and flanking introns of BRCA1 and BRCA2 (≈1,700) and Lynch syndrome/polyposis genes MLH1, MSH2, MSH6, APC, MUTYH, and EPCAM (≈2,200). We validated the microarray with 990 samples previously tested for LR status in BRCA1, BRCA2, MLH1, MSH2, MSH6, APC, MUTYH, or EPCAM. Microarray results were 100% concordant with previous results in the validation studies. Subsequently, clinical microarray analysis was performed on samples from patients with a high likelihood of HBOC mutations (13,124), Lynch syndrome mutations (18,498), and polyposis syndrome mutations (2,739) to determine the proportion of LRs. Results Our results demonstrate that LRs constitute a substantial proportion of genetic mutations found in patients referred for hereditary cancer genetic testing. Conclusion The use of microarray comparative genomic hybridization (CGH) for the detection of LRs is well-suited as an adjunct technology for both single syndrome (by Sanger sequencing analysis) and extended gene panel testing by next generation sequencing analysis. Genetic testing strategies using microarray analysis will help identify additional patients carrying LRs, who are predisposed to various hereditary cancers. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink