PDX Breast Cancer Model WHIM23

Technical Information
Published in Cell Reports, WHIM23 is a highly characterized, HER2-, ER+, PR+ PDX model of breast cancer. Derived from a node metastasis, this line possesses a Y537S mutation in ESR1, a C182X mutation in p53, and an E542K mutation in PIK3CA. WHIM23 and WHIM20 are derived from the same patient.

Technical Data

Whole Genome Sequenced
No
RNA Sequence
No

Tumor Information

Availability
Available
Tumor Site
Metastasis: Node
Patient Number
20

Patient Demographics

Age at Diagnosis
36
Patient Race
Caucasian
Family History
Mother

PAM50 Subtype

PAM50 Originating Tumor
N/A
PAM50 Early Passage
Luminal A
PAM50 Late Passage
Luminal B

Genotype/Mutations

ER Status
Positive
PR Status
Positive
HER2 Status
Negative
p53 Genotype
C182X
PIK3CA Genotype
E542K
ESR1 Genotype
Y537S
Phosphoprotein Highest Rank
Rb_pS807_S811

Pathology

Specimen Type
Punch -- skin right clavicle
Clinical Stage, Diagnosis
N/A
Pathological Stage
3A
Sample Stage
4
Pathology
Ductal; Lobular
Tumor Grade
1
Metastatic Site List
Nodes; Skin
Systemic Treatments
Adjuvant docetaxol, carboplatin alternating with epirubicin, cyclophosphomide x4 cycles; radiation; tamoxifen; first recurrence; docetaxol, carboplatin; Letrozole; fulvestrant; vinorelbine, capecitabine; capecitabine, fulvestrant; capecitabine; paclitaxel, bevacizumab , bev held multiple times; paclitaxel; Grafted sample for WHIM20; IMC-A12, temsirolimus on study; exemestane; Grafted sample for WHIM23; estradiol; doxorubicin liposomal; methotrexate, cyclophosphomide; radiation to right face and neck; eribulin
Overall Survival (months)
97

PAM50 Subtype Expression

PAM50 Microarray Validation
PDX Breast Cancer Model WHIM23 - PAM50 Microarray Validation
Validation of PAM50 microarray. Coclustering of 250 human breast samples representing all the PAM50 intrinsic subtypes and 22 HIM models using the 50 PAM50 genes. Gene expression data of all samples has been obtained using 244K Agilent microarrays.
Claudin Low Signature
PDX Breast Cancer Model WHIM23 - Claudin Low Signature
Microarray of 807 genes that make up the Claudin-low signature. On the right, the expression of each gene (up- or downregulated) of the Claudin-low signature is shown. The two Claudin-low samples (WHIM12 and WHIM17) are identified below the array tree.

ER, HER2 and PR Expression

ER and HER2 Western Blots
PDX Breast Cancer Model WHIM23 - ER and HER2 Western Blots
ER and HER2 protein expression. Tumor lysates from ER-positive (A) and ER-negative (B) WHIM lines were analyzed by western blot to confirm ER and HER2 status. Lysates from ER-negative WHIM lines were also probed with antibodies against the cytokeratin 5/6 (CK 5/6) and CD44 markers. The MCF7 (ER-positive), SKBR3 (ER-negative, HER2-positive) and MDA-MB-231 (ER-negative, CD44-positive) breast cancer cell lines were included as blotting controls.

Circos Plots & Phosphoprotein Expression

Phosphoprotein Expression
PDX Breast Cancer Model WHIM23 - Phosphoprotein Expression
Phosphoprotein expression by RPPA. The RPPA data for WHIM samples and 386 TCGA samples were combined after standardizing the data for each marker (i.e., subtracting the mean and then divided by the standard deviation) in the separate data sets. The combined samples were hierarchically clustered using a Pearson correlation based distance matrix ((1-rho)/2, where rho is the Pearson correlation matrix) and the “ward” linkage based on Ward’s minimum variance. In every case the samples from each WHIM line clustered adjacently, including the two double PDX model isolations (WHIM2 and WHIM5, WHIM20 and WHIM23). This demonstrates that intra-PDX heterogeneity was considerably less than the inter-tumoral heterogeneity in a large RPPA data set and was relatively stable over time and passage.
Protocols & Documents
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