Comprehensive Genomic Profiling of PDX Models

Each model underwent analysis using the Illumina Infinium Omni2.5Exome-8 v1.3 or v1.4 or the Affymetrix SNP 6.0 array. These samples were processed according to PDXnet specifications^{1 (link)} using the tumor-only procedure outlined by recommendations in ASCAT^{62 (link)}. To account for median-centered differences between the Affymetrix and Illumina chip we calculated platform specific thresholds for amplifications and deletions (0.9 and −0.9 for Affymetrix CN ratios, and 0.6 and −0.6 for Illumina CN ratios; ED Figure 3). The gene set chosen for Figure 1a was curated from a set of four breast cancer or pan-cancer publications^{63 (link),64 (link)} as well as sentinel genes, i.e., genes that represent a larger genomic region, from public and commercial sources including FoundationOne, cBioPortal, and Ambry Genetics Corporation. These extra genes include FGF3, CDK12, NOTCH2, H3P6, SIPA1L3, ADCY9, FAM72C, SDK2, CDK18, STX4, TNFRSF10C, NKX3–1, LYN, JAK1, JAK2, CD274, PDCD1LG2, ERBB4, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, MRE11A, MUTYH, NBN, NP1, PALB2, RAD50, RAD51C, and RAD51D.

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Guillen K.P., Fujita M., Butterfield A.J., Scherer S.D., Bailey M.H., Chu Z., DeRose Y.S., Zhao L., Cortes-Sanchez E., Yang C.H., Toner J., Wang G., Qiao Y., Huang X., Greenland J.A., Vahrenkamp J.M., Lum D.H., Factor R.E., Nelson E.W., Matsen C.B., Poretta J.M., Rosenthal R., Beck A.C., Buys S.S., Vaklavas C., Ward J.H., Jensen R.L., Jones K.B., Li Z., Oesterreich S., Dobrolecki L.E., Pathi S.S., Woo X.Y., Berrett K.C., Wadsworth M.E., Chuang J.H., Lewis M.T., Marth G.T., Gertz J., Varley K.E., Welm B.E, & Welm A.L. (2022). A human breast cancer-derived xenograft and organoid platform for drug discovery and precision oncology. Nature Cancer, 3(2), 232-250.

Publication 2022

Infinium Omni2.5Exome-8 v1.3 or v1.4 SNP 6.0 array

Adcy9 Brca1 Brca2 Cancer Cancer of breast Cd274 Cdh1 Chek2 Chip Deletions Genes Genomic Jak1 Jak2 Mre11a Mutyh Notch2 Palb2 Rad50 Rad51c Tnfrsf10c Tumor

Corresponding Organization :

Other organizations : University of Utah, Huntsman Cancer Institute, Magee-Womens Research Institute, UPMC Hillman Cancer Center, University of Pittsburgh, Baylor College of Medicine, Jackson Laboratory

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Variable analysis

independent variables

Affymetrix SNP 6.0 array
Illumina Infinium Omni2.5Exome-8 v1.3 or v1.4 array

dependent variables

Gene copy number amplifications and deletions

control variables

Tumor-only procedure outlined by recommendations in ASCAT
Platform-specific thresholds for amplifications and deletions (0.9 and -0.9 for Affymetrix CN ratios, and 0.6 and -0.6 for Illumina CN ratios)

controls

Positive control: Not specified
Negative control: Not specified

Annotations

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