the HCC1569 breast cancer cell line was derived from a primary ductal breast carcinoma of a 72 year old African American patient. The cell line is HER2 positive and ER negative and has been classified as a basal A type of breast cancer. The STR profile along with other data and references pertinent to this cell line can be found here at Cellosaurus, or here at COSMIC or here at DepMap portal.
The tables below were derived using the data mining tools on the SLKBase and are designed to provide rapid summaries of the oncogene signature of this cell line, and the best druggable targets for these cells.
Oncogene Signature: The Oncogene Signature shows that these cells have amplification and overexpression of ERBB2 and yet the gene was not a hit in the RNAi screen, though its score is fairly close to the cutpoint which does point to some degree of essentiality of this gene, though as shown below, the cells are not at all sensitive to ERBB2 targeted drugs. The PTPN1 gene is amplified and overexpressed and was a hit in the screen, though this is not associated with any drug sensitivity. CCNE1 is amplified and highly overexpressed and the cells have both TP53 and PTEN mutations the latter of which may account for the relative lack of ERBB2 essentiality.
| Gene | CRISPR score | Demeter score | Log fold change | DNA amp | mutation | occ. In Cosmic |
| PTPN1 | -0.535614212 | 2.932419969 | 1.9785 | |||
| CDKN1A | -0.514259695 | -1.669218869 | 1.3762 | |||
| TOP1 | -0.410476598 | 1.11338254 | 1.3752 | |||
| ERBB2 | -0.384407802 | 5.340965441 | 4.8823 | |||
| CCNE1 | -0.37491035 | 4.410121876 | 3.8 | |||
| VEGFA | -0.246801118 | 2.156889608 | 1.0278 | |||
| PTEN | -0.226623391 | -1.972609619 | -0.2532 | p.L265fs | 55 | |
| AGO2 | -0.221520697 | 1.416925394 | 1.3622 | |||
| CCND3 | -0.213111652 | 1.147583182 | 1.0278 | |||
| RECQL4 | -0.142383638 | 1.442934007 | 1.3593 | |||
| TP53 | -0.117281568 | -2.361883566 | -0.0948 | p.E294*, p.S227fs | 23 | |
| PLCG1 | -0.105373317 | 1.824972157 | 1.3752 | |||
| SRC | -0.062236461 | 2.270587012 | 1.3752 | |||
| INPP4A | -0.03223346 | 1.213592743 | 1.9112 | |||
| NF1 | 0.015505382 | 0.395928098 | 0.1092 | NA | 8 | |
| EZH2 | 0.022096032 | 1.042072561 | 1.215 | |||
| MAP2K4 | 0.102993324 | -0.210894427 | -0.104 | p.P338L | 7 |
This is a HER2 amplified cell line that is resistant to all ERBB2 targeted drugs and ERBB2 was not a hit in the RNAi screen, which is consistent with their relative insensitivity to ERBB2 targeted drugs. Is this resistance because of the high level overexpression of AKT3? The cells are sensitive to an AKT3 targeted drug, which is amazing. In Tier 2 the reasonable sensitivity to the CHEK1 drug should be interpreted in the light of the fact that this gene is a common essential in the CRISPR screen and close to being a common essential in the RNAi screen (Demeter). These cell are however sensitive to the BCL2L1 targeted drugs in Tier 2. Thus, in these cells, AKT3 and BCL2L1 are the best druggable targets despite the amplification of ERBB2 in these cells.
| HCC1569.T1 | |||||||||
| Drug name | Gene symbol_HGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit | ||
| Uprosertib | AKT3 | 0 | -1.988875 | 0.8074 | 3.482278896 | p.G477G | 0 | ||
| HCC1569.T2 | |||||||||
| Drug name | Gene symbol_HGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit | achilles_score | demeter |
| AZD7762 | CHEK1 | 0.932482 | -1.836214 | 0.381 | 1.098288953 | NULL | 0 | NULL | -0.555422714 |
| Navitoclax | BCL2L1 | -1.404918 | -1.687592 | 0.8367 | -0.25002983 | NULL | 0 | NULL | -1.938556575 |
| HCC1569T3 | |||||||||
| Drug name | Gene SymbolHGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit | achilles_score | demeter |
| Uprosertib | AKT3 | 0 | -1.988875 | 0.8074 | 3.482278896 | p.G477G | 0 | NULL | -0.014779074 |
| Uprosertib | AKT1 | 0 | -1.988875 | -0.4259 | -0.24654551 | NULL | 0 | NULL | -0.331197766 |
| Uprosertib | AKT2 | 0 | -1.988875 | -0.6927 | -0.11273555 | NULL | 0 | NULL | 0.094668757 |
| CHIR-99021 | GSK3A | -2.129157 | 0 | -0.4796 | -0.04860785 | NULL | 0 | NULL | 0.170014644 |
| CHIR-99021 | GSK3B | -2.129157 | 0 | 0.5503 | 0.375756334 | NULL | 0 | NULL | 0.328850851 |
