The ZR7530 breast cancer cell line

The ZR7530 breast cancer cell line is an ER-positive, HER2 positive breast cancer cell line belonging to the HER2 amp molecular sub-type.  The cell line was derived from the malignant ascites of a 47 year old female of predominantly (75%) African American heritage.  The STR profile along with other genomic data and information pertinent to this cell line can be found here at Cellosaurus, or here at COSMIC, or here at DepMap portal.

Oncogene Signature: In this cell line, ESR1 is highly overexpressed and was found to be esssential in the RNAi based screen, and ERBB2 is amplified and overexpressed and was also found to be a screen hit.  One point mutation in the IKZF1 gene was also identified but was not a hit in the screen.

Gene CRISPR score Demeter score Log fold change DNA amp mutation occ. In Cosmic
ESR1 -0.721298992 2.601489172 -0.3102
ERBB2 -0.594201213 5.695009161 4.2171
IKZF1 -0.212277965 -0.013805798 0.1504 p.R328R 31
IKZF3 -0.068886212 1.186621672 3.7486
MSI2 0.015891257 2.037409709 1.3442
PPM1D 0.067761644 3.261069593 4.0598

ZR7530 drug sensitivities.  In this cell line, ERBB2 is a functional druggable oncogene, and indeed, the cells are quite sensitive to several specific and pan-ERBB specific targeted drugs.  What is most interesting about this cell line however, is the fact that despite the essentiality of ESR1 in these cells, they are actually quite resistant to all ER-targeted drugs.   Under standing the mechanism for that resistance in the face of the essentiality of the gene could provide insight into mechanisms of resistance to ER targeted drugs, particularly if it is related to the ERBB status of the cells.

ZR7530.T1
Drug name Gene symbol_HGNC z_score_GDSC1 z_score_GDSC2 DNA_amp lfc mutation COSMIC_hit
Afatinib ERBB2 -2.084303 -1.820938 4.2171 5.695009161 NULL 0
Lapatinib ERBB2 0 -1.688538 4.2171 5.695009161 NULL 0
ZR7530.T2
None
ZR7530.T3
Drug name Gene SymbolHGNC z_score_GDSC1 z_score_GDSC2 DNA_amp lfc mutation COSMIC_hit achilles_score demeter
Afatinib EGFR -2.084303 -1.820938 0.1504 -3.425858837 NULL 0 NULL 0.052392849
Lapatinib EGFR 0 -1.688538 0.1504 -3.425858837 NULL 0 NULL 0.052392849