The HCC1954 breast cancer cell line was derived from the primary ductal breast carcinoma of a 61 year old female, 71% South Asian (Indian) ancestry and and 29% European Ancestry. As described in more detail below, there is some confusion regarding the oncogene signature of this breast cancer cell line. According to DepMap portal, which is the source of our database, this cell line is an ER-negative, HER2 positive cell line, which also has a PIK3CA mutation. The ERBB2 amplification is reported in DepMap portal and therefore in our database. It is also reported in COSMIC but is not reported in the Cellosaurus data set. With this caveat in mind, one can access the complete genomic information and other data relevant to this cell line here at Cellosaurus, or here at COSMIC, or here at DepMap Portal.
Oncogene Signature: As can be seen below, the Oncogene Signature of this cell line is complex with genomic alterations occurring in several bone fide candidate oncogenes and several of these genes were screen hits and are thus considered to be functional driving oncogenes in this cell line. For convenience, the oncogenes in the table are rank ordered by gene amplification status. You should note in the table below that the high level amplification and overexpression of ERBB2 is shown, but this gene was NOT a hit in either functional screen. You should also note that despite this, HCC1954 cells are highly sensitive to the HER2-specific targeted drug CP724714. Based on this, one should proceed with caution when using this cell line because with respect o their drug sensitivity, these cells behave as if they do have an ERBB2 amplification, and if that is true, then the screen data represent a false negative. The genes highlighted in red are the oncogenes that were hits in one or both of the essentiality screens and thus are considered functional driving oncogenes for this cell line.
| Gene | CRISPR score | Demeter score | Log fold change | DNA amp | mutation | occ. In Cosmic |
| ERBB2 | -0.078244626 | -0.270205987 | 6.144312601 | 6.0173 | ||
| TRIP13 | -0.683287139 | -0.317368668 | 4.126510081 | 3.5338 | ||
| FGFR4 | -0.551232281 | 0.045565143 | 1.761677701 | 2.6573 | ||
| RAD21 | -1.005765284 | 0 | 2.155604719 | 2.3375 | ||
| CCND1 | -0.673129226 | -0.168337389 | 1.657700792 | 2.2888 | ||
| SDHA | -0.779501379 | 0.063729659 | 1.326994863 | 2.0769 | ||
| NSD1 | -0.595455604 | -0.025811226 | 1.977176886 | 1.9758 | ||
| PDCD1LG2 | -0.326077021 | -0.030856028 | 1.705181769 | 1.8939 | ||
| CD274 | -0.111762784 | 0.033679587 | 2.930069269 | 1.8939 | ||
| JAK2 | 0.17472004 | -0.082301706 | 2.522712978 | 1.8939 | ||
| SMARCA2 | 0.19978955 | -0.141255208 | 2.137331735 | 1.5043 | ||
| GNAS | -0.255488491 | -0.090450179 | 1.177736359 | 1.4853 | ||
| MRE11 | -0.931373552 | -0.02400568 | 2.446797312 | 1.4604 | ||
| SESN3 | -0.232805498 | 0 | 1.580047938 | 1.4604 | ||
| YAP1 | -0.495853511 | -0.10297869 | 2.140745546 | 1.3066 | ||
| BIRC3 | 0.165919942 | -0.11950746 | 2.195905656 | 1.3066 | ||
| UBR5 | -0.469968718 | -0.09838702 | 1.009778304 | 1.2236 | ||
| AURKA | -0.921846862 | -0.281343612 | 1.720770594 | 1.0308 | ||
| BCL9 | 0.248491324 | -0.132098297 | 1.301452918 | 1.0013 | ||
| PIK3CA | -0.680242059 | -0.038079112 | 0.713827456 | 0.3852 | p.H1047R | 1582 |
| TP53 | 0.026983961 | -0.112775117 | 1.4930406 | -0.1317 | p.Y163C | 183 |
HCC1954 Drug sensitivities. As this is a cell line with high level amplification of ERBB2, it is not surprising that the cells are exquisitely sensitive to CP724714. However, it is surprising that these cells did not exhibit any sensitivity toward any other ERBB2 targeted drug in either the GDSC1 or GDSC2 data sets. So, something is off here. Either the screen data from both screens are incorrect, or the screen data truly show that ERBB2 is not essential despite it’s amplification, then that suggests that the CP sensitivity detected in the GDSC1 data set is incorrect. There are other interesting drug sensitivities in Tier 2 with drug sensitivity being associated with essentiality in the screens. In Tier 3, this time the cells exhibit high sensitivity to the PORCN targeted drugs but only in the GDSC2 data set which is opposite of what has been seen in other cell lines. The cells are moderately sensitive to a pan-specific AKT drug, and also to a pan-specific PIM kinase targeted drug. Thus, anyone wanting to use this cell line to develop potential drug combinations should validate the sensitivity to ERBB2 targeted drugs first.
| HCC1954.T1 | |||||||||
| Drug name | Gene symbol_HGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit | ||
| CP724714 | ERBB2 | -2.104601 | 0 | 6.0173 | 6.144312601 | NULL | 0 | ||
| HCC1954.T2 | |||||||||
| Drug name | Gene symbol_HGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit | achilles_score | demeter |
| ML323 | WDR48 | 0 | -1.829971 | -0.1573 | 0.659747657 | NULL | 0 | -0.585641944 | 0 |
| SL0101 | AURKB | -2.662791 | 0 | -0.1317 | 0.661135901 | NULL | 0 | -1.304477935 | -0.694930727 |
| HCC1954.T3 | |||||||||
| Drug name | Gene SymbolHGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit | achilles_score | demeter |
| OF-1 | BRD1 | 0 | -2.868482 | -1.1109 | -0.415594307 | NULL | 0 | -0.369620484 | -0.048301797 |
| OF-1 | BRPF1 | 0 | -2.868482 | -0.1266 | 0.071100192 | NULL | 0 | -0.30882967 | 0.100957972 |
| Wnt-C59 | PORCN | -0.196824 | -2.207411 | 0.6075 | 0.659115257 | NULL | 0 | 0.033157083 | 0 |
| LGK974 | PORCN | 0.042257 | -1.503147 | 0.6075 | 0.659115257 | NULL | 0 | 0.033157083 | 0 |
| GSK690693 | AKT1 | -1.652801 | 0 | -0.1302 | -0.244394593 | NULL | 0 | 0.2278855 | 0.056082099 |
| GSK690693 | AKT2 | -1.652801 | 0 | -0.0646 | 0.726384418 | NULL | 0 | -0.053098878 | 0.076032243 |
| GSK690693 | AKT3 | -1.652801 | 0 | 0.365 | -1.27917005 | NULL | 0 | 0.154344339 | 0.097165701 |
| SL0101 | PIM1 | -2.662791 | 0 | 0.1833 | 1.798817462 | NULL | 0 | 0.425443217 | -0.034700356 |
| SL0101 | PIM3 | -2.662791 | 0 | -1.1109 | -1.180827428 | NULL | 0 | 0.002287772 | -0.343662105 |
