Histology and genomic copy number alterations in TRAMP tumors.

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Histology and genomic copy number alterations in TRAMP tumors. Histology and genomic copy number alterations in TRAMP tumors. A–B', representative microscopic images from H&E-stained TRAMP sections from the prostate glands from which DNA was extracted for CGH analysis. A–A', TRAMP atypical hyperplasia of Tag (AHTag) at low (4×) and high-power (20×), respectively. B–B', TRAMP NEC at low (4×) and high-power (20×), respectively. C, copy number alterations (CNAs) in TRAMP mice by array CGH. Genomic DNA from C57BL/6. FVB TRAMP prostate neuroendocrine carcinomas, AHTag lesions, and spleen germline DNA control were hybridized against sex-matched normal mouse C57BL/6 reference DNA using Agilent CGH slides containing 180K probes. Whole genome view of overlaid moving averages (2 Mb window) for the log2 ratios of fluorescence between a sample/reference DNA probe (y- axis) plotted at its genomic position (x-axis), red, blue, and yellow (neuroendocrine tumors; n = 3), cyan blue shades (AHTag n = 2), and green shades (germline n = 3). Aberrations called in any samples (germline and tumor) by the ADM-2 algorithm are identified by a horizontal bar (red, blue, and yellow: neuroendocrine tumors), cyan (AHTag), and green (germline DNA). Aberrations present in at least two (of 3) neuroendocrine tumors are indicated by arrows; those found in individual mice are indicated by arrowheads. (1) Representative CNVs in common between germline, AHTag and neuroendocrine tumors; (2) aberrations called by the ADM-2 algorithm in a single sample that by manual inspection exhibited similar fluorescence intensities in all samples including germline and tumor (see Supplementary Fig. S2, for representative examples); (3) example of a known strain-specific alteration in the FVB strain (a copy number loss in the T-cell receptor V-beta gene segment (chr6:41,018,389-41,112,757). D, zoom-in view of chromosome 6 showing overlaid data points for log2 ratios of the Grid2 gene region. Green, values below log2 = −0.25; red: values above log2 = 0.25. Top, spleen and AHTag samples. Bottom, neuroendocrine tumors showing a SCNAs in the Grid 2 gene. Aberrations called by the ADM-2 algorithm are identified by a horizontal line (bottom). E, zoom-in on whole chromosome 19 showing overlaid data points for log2 ratios. Green: values below log2 = −0.25; red: values above log2 = 0.25. Top, spleen and AHTag samples. Bottom, neuroendocrine tumors showing a copy number loss of whole chr19. The aberration called by the ADM-2 algorithm of the entire chromosome 19 is identified by a horizontal line (bottom). Daniella Bianchi-Frias et al. Mol Cancer Res 2015;13:339-347 ©2015 by American Association for Cancer Research