The Hs578T human breast cancer cell line was derived from an invasive ductal carcinoma of a 74 year old Caucasian female. The specimen and cell line are ER and HER2 negative and the cell line has been classified as a Basal B type breast cancer cell line. The STR profile along with other genomic information pertinent to this cell line can be found here at Cellosaurus and here at DepMap portal. There is no entry for this cell line in COSMIC.
Oncogene Signature: This Basal B breast cancer cell line, like HMC18 is characterized by RAS and TP53 mutations. In this case, it is HRAS that is mutated. These cells also have a PIK3R1 point mutation and this gene along with HRAS were hits in the CRISPR screen, making them functional driving oncogenes for this cell line.
| Gene | CRISPR score | Demeter score | Log fold change | DNA amp | mutation | occ. In Cosmic |
| HRAS | -0.818862674 | -0.474283815 | -0.092855201 | -0.204732 | p.G12D | 309 |
| PIK3R1 | -0.511800455 | -0.040595737 | -0.737789796 | -0.29739 | p.90_91insN | 10 |
| TP53 | 0.338436268 | -0.24112858 | 0.328302008 | 0.239598 | p.V157F | 231 |
| NF1 | 0.37415158 | 0.878839826 | 0.012692659 | -0.250199 | p.G2745R | 14 |
Hs578T drug sensitivities. This Basal B breast cancer cell line is characterized by driving oncogenes with point mutations, and given that it is a Basal B cell line, it presents a plethora of targeted drug opportunities although these drug sensitivities are associated with high level overexpression of the target in the absence of gene amplification. Accordingly, PDGFRA, PDGFRB, MET, AKT3 and PIK3D are all overexpressed at the message levels in these cells and this overexpression is associated with significant sensitivity to cognate targeted drugs. Tier 2 contains different drugs that target BRD family members as well as two genes that regulate apoptosis, and a PLK1 targeted drug as this gene was a hit in both screens. Finally, Tier 3 shows that the cells are sensitive to other pan-specific inhibitors of cell signaling molecules including MAPK1/2 targeted drugs, and this is likely connected to the HRAS mutation in these cells.
| Hs578T.T1 | |||||||||
| Drug name | Gene symbol_HGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit | ||
| Dasatinib | PDGFRA | 0 | -1.775872 | -0.270467 | 4.773247068 | NULL | 0 | ||
| Dasatinib | PDGFRB | 0 | -1.775872 | 0.17698 | 6.52642269 | NULL | 0 | ||
| BIBF-1120 | PDGFRB | -1.772954 | 0 | 0.17698 | 6.52642269 | NULL | 0 | ||
| BIBF-1120 | PDGFRA | -1.772954 | 0 | -0.270467 | 4.773247068 | NULL | 0 | ||
| JNJ38877605 | MET | -1.959352 | 0 | 0.268729 | 2.237529787 | NULL | 0 | ||
| AT7867 | AKT3 | -2.046345 | 0 | -0.285223 | 3.990496123 | NULL | 0 | ||
| IC-87114 | PIK3CD | -1.840778 | 0 | 0.24309 | 2.319562434 | NULL | 0 | ||
| Hs578T.T2 | |||||||||
| Drug name | Gene symbol_HGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit | achilles_score | demeter |
| BI-2536 | PLK1 | 0 | -2.053759 | -0.354953 | -0.213113687 | NULL | 0 | -1.941747241 | -0.928182802 |
| JQ1 | BRD2 | 0.82121 | -2.024824 | 0.547299 | 0.289323946 | NULL | 0 | -0.540353265 | -0.372138688 |
| JQ1 | BRD4 | 0.82121 | -2.024824 | 0.190158 | 0.623256028 | NULL | 0 | -1.097538234 | -0.845400961 |
| RVX-208 | BRD4 | 0 | -1.912375 | 0.190158 | 0.623256028 | NULL | 0 | -1.097538234 | -0.845400961 |
| OTX015 | BRD2 | 0 | -1.702728 | 0.547299 | 0.289323946 | NULL | 0 | -0.540353265 | -0.372138688 |
| OTX015 | BRD4 | 0 | -1.702728 | 0.190158 | 0.623256028 | NULL | 0 | -1.097538234 | -0.845400961 |
| UMI-77 | MCL1 | 0 | -1.506285 | -0.285223 | -0.227417586 | NULL | 0 | -0.80575789 | 0.105047353 |
| RO-3306 | CDK1 | -2.415834 | -1.4845 | -0.276063 | -0.648612938 | NULL | 0 | -1.868407345 | -1.200785704 |
| TW 37 | BCL2L1 | -1.516715 | 0 | 0.273178 | -0.293639736 | NULL | 0 | -0.713464221 | -0.353292959 |
| TW 37 | MCL1 | -1.516715 | 0 | -0.285223 | -0.227417586 | NULL | 0 | -0.80575789 | 0.105047353 |
| Hs578T.T3 | |||||||||
| Drug name | Gene SymbolHGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit | achilles_score | demeter |
| BI-2536 | PLK2 | 0 | -2.053759 | 0.228914 | -0.245735933 | NULL | 0 | -0.080433268 | -0.056430486 |
| BI-2536 | PLK3 | 0 | -2.053759 | 0.272912 | 0.597804021 | NULL | 0 | -0.084415574 | -0.140353554 |
| JQ1 | BRD3 | 0.82121 | -2.024824 | -0.322747 | -1.089034374 | NULL | 0 | 0.231550196 | 0.242716926 |
| JQ1 | BRDT | 0.82121 | -2.024824 | 0.272912 | 0.084064265 | NULL | 0 | 0.050956679 | -0.026372201 |
| Dasatinib | ABL1 | 0 | -1.775872 | -0.322747 | 1.145847141 | NULL | 0 | -0.314462089 | -0.091449311 |
| Dasatinib | KIT | 0 | -1.775872 | -0.270467 | 0.033182469 | NULL | 0 | -0.148821933 | 0.194457856 |
| Dasatinib | PDGFRA | 0 | -1.775872 | -0.270467 | 4.773247068 | NULL | 0 | -0.458559989 | -0.076478844 |
| Dasatinib | PDGFRB | 0 | -1.775872 | 0.17698 | 6.52642269 | NULL | 0 | -0.294120509 | 0.031932563 |
| Dasatinib | SRC | 0 | -1.775872 | 0.273178 | 0.024960373 | NULL | 0 | -0.043128946 | -0.114169899 |
| OTX015 | BRD3 | 0 | -1.702728 | -0.322747 | -1.089034374 | NULL | 0 | 0.231550196 | 0.242716926 |
| PD0325901 | MAP2K1 | -1.662105 | -0.070282 | -0.290036 | 0.760346716 | NULL | 0 | -0.141241774 | -0.123419411 |
| PD0325901 | MAP2K2 | -1.662105 | -0.070282 | 0.190158 | 0.731159362 | NULL | 0 | -0.227274275 | -0.248798414 |
| AT7867 | AKT1 | -2.046345 | 0 | -0.267507 | -0.163991905 | NULL | 0 | -0.284645629 | -0.091902912 |
| AT7867 | AKT2 | -2.046345 | 0 | 0.181617 | -0.139007572 | NULL | 0 | -0.193304242 | -0.043299616 |
| AT7867 | AKT3 | -2.046345 | 0 | -0.285223 | 3.990496123 | NULL | 0 | 0.090568539 | 0.069876348 |
| BIBF-1120 | KDR | -1.772954 | 0 | -0.270467 | 0.093976148 | NULL | 0 | -0.243202382 | 0.276992995 |
| BIBF-1120 | PDGFRA | -1.772954 | 0 | -0.270467 | 4.773247068 | NULL | 0 | -0.458559989 | -0.076478844 |
| BIBF-1120 | PDGFRB | -1.772954 | 0 | 0.17698 | 6.52642269 | NULL | 0 | -0.294120509 | 0.031932563 |
