The HCC2218 breast cancer cell line was derived from primary ductal breast carcinoma of a 38 year old Caucasian female. The cell line contains a HER2 (ERBB2) gene amplification and is ER-negative. Consistent with the ERBB2 gene amplification, the molecular profile of the cell line conforms to being classified as of the HER2 subtype. The STR profile for this cell line along with other genomic data pertinent to the cell line can be found here at Cellosaurus, or here at COSMIC or here at DepMap portal.
Oncogene Signature: Note that the oncogene signature shown below indicates the presence of the ERBB2 amplification and overexpression and the shRNA screen for this cell line yielded a result that was close to the cut point used to consider the gene a screen hit, but still slightly below the -0.5 value used to determine gene essentiality. Interestingly, none of the other alterations in candidate oncogenes were associated with gene essentiality in the shRNA screen. Once again, there is a discrepancy between the genomic features of this cell line as indicated in Expasy and that in DepMap portal. Expasy indicates the presence of a TP53 mutation in this cell line as well as a MET point mutation, and neither of those features appear in DepMap portal and therefore in our database. Please consider this carefully when working with this cell line.
| Gene | CRISPR score | Demeter score | Log fold change | DNA amp | mutation | occ. In Cosmic |
| ERBB2 | -0.412879752 | 5.085926364 | 3.5235 | |||
| RECQL4 | -0.10059711 | -1.204722084 | 1.1268 | |||
| PARP1 | -0.08170007 | 1.055490905 | 1.8131 | |||
| HOXB13 | -0.070653574 | 2.08746284 | 3.671 | |||
| PPM1D | 0.029978066 | 2.199303152 | 3.333 | |||
| BRIP1 | 0.063052323 | 2.162543516 | 3.9871 | |||
| AKT3 | 0.085806969 | -1.615037336 | 1.0438 | |||
| LYN | 0.203157347 | -2.832727412 | 1.0047 |
HCC2218 drug sensitivities. Despite the observation that the essentiality score for the ERBB2 oncogene fell just below the cut-point that is used to identify screen hits, the drug sensitivity data show clearly that this gene is highly essential in this cell line. Not only are the cells sensitive to several ERBB2 targeted drugs as shown in Tier 1 (Note the Z-score for the ERBB2-specific inhibitor CP724714!) Indeed, there are no drugs in the Tier 2 category, and most of the drugs in Tier 3 are pan-specific ERBB drugs that inhibit ERBB2. Interestingly, the cells are also sensitive to other pan-specific cell signaling inhibitors.
| HCC2218.T1 | |||||||||
| Drug name | Gene symbol_HGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit | ||
| Afatinib | ERBB2 | -3.149726 | -3.384194 | 3.5235 | 5.085926364 | NULL | 0 | ||
| Lapatinib | ERBB2 | -5.01911 | -2.082584 | 3.5235 | 5.085926364 | NULL | 0 | ||
| PF-00299804 | ERBB2 | -3.21387 | 0 | 3.5235 | 5.085926364 | NULL | 0 | ||
| CI-1033 | ERBB2 | -2.40595 | 0 | 3.5235 | 5.085926364 | NULL | 0 | ||
| CP724714 | ERBB2 | -6.512228 | 0 | 3.5235 | 5.085926364 | NULL | 0 | ||
| HCC2218.T2 | |||||||||
| None | |||||||||
| HCC2218.T3 | |||||||||
| Drug name | Gene SymbolHGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit | achilles_score | demeter |
| Afatinib | EGFR | -3.149726 | -3.384194 | 0.062 | -0.154513545 | NULL | 0 | NULL | -0.111533845 |
| Lapatinib | EGFR | -5.01911 | -2.082584 | 0.062 | -0.154513545 | NULL | 0 | NULL | -0.111533845 |
| Sorafenib | KDR | -0.937957 | -1.537279 | -0.0037 | 0.145050333 | NULL | 0 | NULL | 0.16034598 |
| Sorafenib | KIT | -0.937957 | -1.537279 | -0.0037 | -0.089965762 | NULL | 0 | NULL | 0.138603238 |
| Sorafenib | PDGFRA | -0.937957 | -1.537279 | -0.0037 | -0.097610797 | NULL | 0 | NULL | -0.047052146 |
| Sorafenib | PDGFRB | -0.937957 | -1.537279 | 0.5337 | -0.173064709 | NULL | 0 | NULL | 0.019536616 |
| Sorafenib | RAF1 | -0.937957 | -1.537279 | -0.3719 | -1.138793972 | NULL | 0 | NULL | 0.027658371 |
| Sorafenib | BRAF | -0.937957 | -1.537279 | 0.317 | -0.839511762 | p.E296K | 0 | NULL | 0.029790454 |
| Pelitinib | EGFR | -2.027723 | 0 | 0.062 | -0.154513545 | NULL | 0 | NULL | -0.111533845 |
| CI-1033 | EGFR | -2.40595 | 0 | 0.062 | -0.154513545 | NULL | 0 | NULL | -0.111533845 |
| PF-00299804 | EGFR | -3.21387 | 0 | 0.062 | -0.154513545 | NULL | 0 | NULL | -0.111533845 |
| AST-1306 | EGFR | -3.135948 | 0 | 0.062 | -0.154513545 | NULL | 0 | NULL | -0.111533845 |
| CI-1033 | ERBB4 | -2.40595 | 0 | -0.3906 | -0.115462448 | NULL | 0 | NULL | -0.164744153 |
| PF-00299804 | ERBB4 | -3.21387 | 0 | -0.3906 | -0.115462448 | NULL | 0 | NULL | -0.164744153 |
| AST-1306 | ERBB4 | -3.135948 | 0 | -0.3906 | -0.115462448 | NULL | 0 | NULL | -0.164744153 |
| Amuvatinib | FLT3 | -2.348674 | 0 | -0.9404 | -0.014213859 | NULL | 0 | NULL | -0.009557283 |
| Amuvatinib | KIT | -2.348674 | 0 | -0.0037 | -0.089965762 | NULL | 0 | NULL | 0.138603238 |
| Amuvatinib | PDGFRA | -2.348674 | 0 | -0.0037 | -0.097610797 | NULL | 0 | NULL | -0.047052146 |
