We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Expression profiling of formalin-fixed paraffin-embedded primary breast tumors using cancer-specific and whole genome gene panels on the DASL® platform.
- Authors
Reinholz, Monica M.; Eckel-Passow, Jeanette E.; Anderson, S. Keith; Asmann, Yan W.; Zschunke, Michael A.; Oberg, Ann L.; McCullough, Ann E.; Dueck, Amylou C.; Beiyun Chen; April, Craig S.; Wickham-Garcia, Eliza; Jenkins, Robert B.; Cunningham, Julie M.; Jin Jen; Perez, Edith A.; Jian-Bing Fan; Lingle, Wilma L.
- Abstract
Background: The cDNA-mediated Annealing, extension, Selection and Ligation (DASL) assay has become a suitable gene expression profiling system for degraded RNA from paraffin-embedded tissue. We examined assay characteristics and the performance of the DASL 502-gene Cancer Panelv1 (1.5K) and 24,526-gene panel (24K) platforms at differentiating nine human epidermal growth factor receptor 2- positive (HER2+) and 11 HER2- negative (HER2-) paraffin-embedded breast tumors. Methods: Bland-Altman plots and Spearman correlations evaluated intra/inter-panel agreement of normalized expression values. Unequal-variance t-statistics tested for differences in expression levels between HER2 + and HER2 - tumors. Regulatory network analysis was performed using Metacore (GeneGo Inc., St. Joseph, MI). Results: Technical replicate correlations ranged between 0.815-0.956 and 0.986-0.997 for the 1.5K and 24K panels, respectively. Inter-panel correlations of expression values for the common 498 genes across the two panels ranged between 0.485-0.573. Inter-panel correlations of expression values of 17 probes with base-pair sequence matches between the 1.5K and 24K panels ranged between 0.652-0.899. In both panels, erythroblastic leukemia viral oncogene homolog 2 (ERBB2) was the most differentially expressed gene between the HER2 + and HER2 - tumors and seven additional genes had p-values < 0.05 and log2 -fold changes > ∣0.5∣ in expression between HER2 + and HER2 - tumors: topoisomerase II alpha (TOP2A), cyclin a2 (CCNA2), v-fos fbj murine osteosarcoma viral oncogene homolog (FOS), wingless-type mmtv integration site family, member 5a (WNT5A), growth factor receptor-bound protein 7 (GRB7), cell division cycle 2 (CDC2), and baculoviral iap repeat-containing protein 5 (BIRC5). The top 52 discriminating probes from the 24K panel are enriched with genes belonging to the regulatory networks centered around v-myc avian myelocytomatosis viral oncogene homolog (MYC), tumor protein p53 (TP53), and estrogen receptor α (ESR1). Network analysis with a two-step extension also showed that the eight discriminating genes common to the 1.5K and 24K panels are functionally linked together through MYC, TP53, and ESR1. Conclusions: The relative RNA abundance obtained from two highly differing density gene panels are correlated with eight common genes differentiating HER2 + and HER2 - breast tumors. Network analyses demonstrated biological consistency between the 1.5K and 24K gene panels.
- Subjects
GENETIC research; ONCOLOGY; NUCLEIC acids; GENETIC regulation; CELL division; OSTEOSARCOMA; TUMOR proteins; TUMOR markers; EPIDERMAL growth factor; DNA topoisomerase II
- Publication
BMC Medical Genomics, 2010, Vol 3, p60
- ISSN
1755-8794
- Publication type
Article
- DOI
10.1186/1755-8794-3-60