Figure 4 from Development and Application of MiMouse, a Comprehensive Genomic Profiling Panel for Credentialing Mouse Tumor Models
Year: 2025
Type: other
Abstract: MiMouse for CGP and genomic credentialing across the neoplastic spectrum of two large cohorts of inducible fallopian tube (ovary) and colorectal (colorectal carcinoma) tumors. A, Promoters and transgenes used in the cohorts. Ovary and colorectal carcinoma tumor cohorts tested by MiMouse. Genes in bold were activated, and those in regular were inactivated; Trp53 (bold gray) was either inactivated through deletion or a point mutation was expressed (see main text for specific models). Abbreviations for genotypes (as used in the heatmap) are indicated. B, MiMouse cohort characteristics and CGP results from the ovary (predominantly HGSC; top, total n = 172) and colorectal carcinoma (bottom, total n = 100) cohorts are shown. Genotype, histology (CRC, carcinoma; eHGSC, early HGSC; HP, hyperplastic; Met., metastasis; MMMT, carcinosarcoma) and model type (GEMM, GEMM tumor tissue) are shown. Gene-level FGA (see main text) is shown according to the color scale (gray indicates no value due to QC failure, see Supplementary Fig. S9). All detected somatic, prioritized, amplifications (red), deep (homozygous) deletions (blue; none detected), and prioritized somatic mutations (black) across the cohorts are shown. C and D, CN plots of two colorectal carcinoma samples with focal amplifications in Myc or Pik3ca (indicated by arrows) are shown. The log2 CNR (vs. pseudo-normal) of individual amplicons are plotted, with genes (different colors) in genome order (chrs on bottom of plot) and gene-level log2 CNR indicated by black bars (black bars). E, CN plots of two histologically distinct HGSC tumors arising from both ovaries of the same mouse (1628LOT_X5 = left; MG1_X33 = right). Shared Myc amplifications are indicated. The remaining somatic CN profile (including gains in Arid1a and Csmd3 and loss of Mtor) is consistent with clonal origin [Trp53 (gray), which includes the engineered flox amplicons lost after induction and is shown for estimation of relative tumor content]. CRC, colorectal carcinoma.
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4415654399