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Feasibility of implementing molecular-guided therapy for the treatment of patients with relapsed or refractory neuroblastoma.

Saulnier Sholler GL, Bond JP, Bergendahl G, Dutta A, Dragon J, Neville K, Ferguson W, Roberts W, Eslin D, Kraveka J, Kaplan J, Mitchell D, Parikh N, Merchant M, Ashikaga T, Hanna G, Lescault PJ, Siniard A, Corneveaux J, Huentelman M, Trent J - Cancer Med (2015)

Bottom Line: Current treatment options for recurrent neuroblastoma are limited and ineffective, with a survival rate of <10%.Clinical benefit was seen in 64% of patients as stabilization of disease for at least one cycle of therapy or partial response.This study demonstrates the feasibility and safety of performing real-time genomic profiling to guide treatment decision making for pediatric neuroblastoma patients.

View Article: PubMed Central - PubMed

Affiliation: Helen DeVos Children's Hospital, Grand Rapids, Michigan.

No MeSH data available.


Related in: MedlinePlus

Exploratory multivariate analysis of combined microarray and RNA-Seq gene expression profiles. (A) Heat map and sample dendrogram. Red indicates relatively high expression while green indicates relatively low expression. The first character of the sample label indicates a GeneChip (G) or an RNA-Seq (R) profile, the following integer indicates the biopsy, and the final two characters (e.g., S3) indicate the biopsy section. (B) Multidimensional scaling. Samples are represented by their biopsy number, colored by the technology (GeneChip, red; RNA-Seq, blue).
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fig03: Exploratory multivariate analysis of combined microarray and RNA-Seq gene expression profiles. (A) Heat map and sample dendrogram. Red indicates relatively high expression while green indicates relatively low expression. The first character of the sample label indicates a GeneChip (G) or an RNA-Seq (R) profile, the following integer indicates the biopsy, and the final two characters (e.g., S3) indicate the biopsy section. (B) Multidimensional scaling. Samples are represented by their biopsy number, colored by the technology (GeneChip, red; RNA-Seq, blue).

Mentions: A reproducibility study was performed within the study to evaluate the variation among multiple biopsy sections from the same tumor. Expression profiling and drug predictions based on triplicate sections were analyzed. Distance-based nonparametric multivariate analysis of variance 33,34 allowed us to reject the hypothesis that variation between biopsies can be accounted for by the variation within biopsies (P = 0.001). That the variation among expression profiles associated with the same biopsy is small compared with the variation between expression profiles associated with different biopsies is also apparent from Multidimensional Scaling (Fig. 3; 19). Similarly, the variation among drug sets associated with the same biopsy was small compared with the variation among drug lists associated with different biopsies (P = 0.001). The reproducibility averaged over patients, replicates, and drugs is 0.68. As the threshold score increased to score >10, the reproducibility increased to 1 35. Table S2 provides the RNA expression profiles for study patients.


Feasibility of implementing molecular-guided therapy for the treatment of patients with relapsed or refractory neuroblastoma.

Saulnier Sholler GL, Bond JP, Bergendahl G, Dutta A, Dragon J, Neville K, Ferguson W, Roberts W, Eslin D, Kraveka J, Kaplan J, Mitchell D, Parikh N, Merchant M, Ashikaga T, Hanna G, Lescault PJ, Siniard A, Corneveaux J, Huentelman M, Trent J - Cancer Med (2015)

Exploratory multivariate analysis of combined microarray and RNA-Seq gene expression profiles. (A) Heat map and sample dendrogram. Red indicates relatively high expression while green indicates relatively low expression. The first character of the sample label indicates a GeneChip (G) or an RNA-Seq (R) profile, the following integer indicates the biopsy, and the final two characters (e.g., S3) indicate the biopsy section. (B) Multidimensional scaling. Samples are represented by their biopsy number, colored by the technology (GeneChip, red; RNA-Seq, blue).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4472210&req=5

fig03: Exploratory multivariate analysis of combined microarray and RNA-Seq gene expression profiles. (A) Heat map and sample dendrogram. Red indicates relatively high expression while green indicates relatively low expression. The first character of the sample label indicates a GeneChip (G) or an RNA-Seq (R) profile, the following integer indicates the biopsy, and the final two characters (e.g., S3) indicate the biopsy section. (B) Multidimensional scaling. Samples are represented by their biopsy number, colored by the technology (GeneChip, red; RNA-Seq, blue).
Mentions: A reproducibility study was performed within the study to evaluate the variation among multiple biopsy sections from the same tumor. Expression profiling and drug predictions based on triplicate sections were analyzed. Distance-based nonparametric multivariate analysis of variance 33,34 allowed us to reject the hypothesis that variation between biopsies can be accounted for by the variation within biopsies (P = 0.001). That the variation among expression profiles associated with the same biopsy is small compared with the variation between expression profiles associated with different biopsies is also apparent from Multidimensional Scaling (Fig. 3; 19). Similarly, the variation among drug sets associated with the same biopsy was small compared with the variation among drug lists associated with different biopsies (P = 0.001). The reproducibility averaged over patients, replicates, and drugs is 0.68. As the threshold score increased to score >10, the reproducibility increased to 1 35. Table S2 provides the RNA expression profiles for study patients.

Bottom Line: Current treatment options for recurrent neuroblastoma are limited and ineffective, with a survival rate of <10%.Clinical benefit was seen in 64% of patients as stabilization of disease for at least one cycle of therapy or partial response.This study demonstrates the feasibility and safety of performing real-time genomic profiling to guide treatment decision making for pediatric neuroblastoma patients.

View Article: PubMed Central - PubMed

Affiliation: Helen DeVos Children's Hospital, Grand Rapids, Michigan.

No MeSH data available.


Related in: MedlinePlus