1. Comprehensive Screening of Gene Copy Number Aberrations in Formalin-Fixed, Paraffin-Embedded Solid Tumors Using Molecular Inversion Probe–Based Single- Nucleotide Polymorphism Array 
Rajesh R. Singh, Meenakshi Mehrotra, Hui Chen, Alaa A. Almohammedsalim, Ayesagul Sahin, Alex Bosamra, Keyur P. Patel, Mark J. Routbort, Xinyan Lu, Abraham Ronald, Bal Mukund Mishra, Shumaila Virani, L. Jeffrey Medeiros, Rajyalakshmi Luthra 
The Journal of Molecular Diagnostics 
Volume 18, Issue 5, Pages (September 2016)
DOI: /j.jmoldx
Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology Terms and Conditions

2. Figure 1
Detection of ERBB2 gene amplifications. The ability of OS MIP array to detect low to high level ERBB2 gene copy number aberrations in a representative set of tumor samples (A) and SKBR3 cell line (B) is shown. For each sample, the amplification of ERBB2 gene loci on chromosome (Chr) 17 is highlighted. Red and blue lines adjacent to the schematic chromosome picture indicate gross loss or gain of the chromosome 17 with high degree of loss (red-both alleles) or high level amplifications (blue) indicated by double lines. ERBB2 copy numbers in each sample by OS MIP array, fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS) are provided along with the tumor cellularity. The position of ERBB2 on the chromosome and the cluster of probes covering it are marked by ovals. Chr, chromosome; CN, copy number; IHC, immunohistochemistry status.
The Journal of Molecular Diagnostics  , DOI: ( /j.jmoldx )
Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology Terms and Conditions

3. Figure 2
Detection of EGFR gene amplifications. Detection of EGFR gene amplifications in a representative set of tumor samples by OS MIP array. EGFR gene copy numbers detected in each sample by OS MIP array and next-generation sequencing (NGS) are provided along with the tumor cellularity. The position of EGFR on the chromosome and the cluster of probes covering it are marked by ovals. Chr, chromosome; CN, copy number.
The Journal of Molecular Diagnostics  , DOI: ( /j.jmoldx )
Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology Terms and Conditions

4. Figure 3
Detection of FGFR1 gene amplifications. Detection of FGFR1 gene amplifications in a representative set of tumor samples with varying degree of tumor cellularity (50% to 80%). The position of FGFR1 on the chromosome and the cluster of probes covering it are marked by ovals. Chr, chromosome; CN, copy number; NGS, next-generation sequencing.
The Journal of Molecular Diagnostics  , DOI: ( /j.jmoldx )
Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology Terms and Conditions

5. Figure 4
Simultaneous detection of multiple copy number aberrations. In a colon cancer sample, the OS MIP array simultaneously detected multiple copy number aberrations across several clinically significant genes, which included amplifications in four oncogenes (top row) and copy number losses in four tumor suppressors (bottom row). This example illustrates the advantages of a genome-wide comprehensive screen provided by the platform with a special focus on 900 cancer-related genes. The position of the genes on their respective chromosomes and the cluster of probes covering them are marked by ovals. Chr, chromosome; CN, copy number; NGS, next-generation sequencing.
The Journal of Molecular Diagnostics  , DOI: ( /j.jmoldx )
Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology Terms and Conditions

6. Figure 5
Limit of detection for gene amplification and loss. The limit of detection of the OS MIP array platform was tested by analyzing sequentially diluted samples of FFPE DNA from the H460 cell line, known to harbor MYC gene amplification and a single gene copy loss of EGFR. A: Alteration of the gene copy numbers in the MYC and EGFR loci observed by OS MIP array. The cluster of probes covering MYC and EGFR are marked by the red and green ovals, respectively. B: The sequential variation of the MYC and EGFR copy numbers in accordance with the level of the H460 cell line DNA dilution illustrates accurate and sensitive detection of both gene amplifications and deletions, respectively. Fluorescence in situ hybridization (FISH) analysis showed H460 cell lines to have a single copy of EGFR and 11.2 copies of MYC. The absolute gene copies expected at each dilution as per FISH are mentioned above each dilution in the figure.
The Journal of Molecular Diagnostics  , DOI: ( /j.jmoldx )
Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology Terms and Conditions

7. Supplemental Figure S1
Genes tested by OncoScan MIP array. The chart summarizes different genes tested for copy number aberrations in this study and the number of samples tested for each gene. A total of 15 genes were tested in a variety of solid tumor types with a focus on genes with established clinical importance.
The Journal of Molecular Diagnostics  , DOI: ( /j.jmoldx )
Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology Terms and Conditions

8. Supplemental Figure S2
Assay workflow. End-to-end (DNA extraction to reporting) workflow for 22 samples along with the details of the steps involved in each day, hands-on time, and the quality control steps and metrics are shown.
The Journal of Molecular Diagnostics  , DOI: ( /j.jmoldx )
Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology Terms and Conditions

9. Supplemental Figure S3
Formalin-fixed, paraffin-embedded DNA extracted from normal brain samples analyzed by OncoScan MIP array shows a normal diploid status without any detectable copy number aberrations, demonstrating the specificity of the platform.
The Journal of Molecular Diagnostics  , DOI: ( /j.jmoldx )
Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology Terms and Conditions