The MDA-MB-453 human breast cancer cell line was derived from a pericardial effusion of a 48 year old Caucasian female previously diagnosed with infiltrating ductal breast carcinoma. There is some confusion as to the classification of this cell line. Both Expasy.org and DepMap Portal are calling this cell line a triple negative line. However, as will be seen in our oncogene signature below, there is a low level amplification of the ERBB2 gene associated with significant overexpression, and the gene was a strong hit in the CRISPR screen, suggesting that this really is an ER-negative, HER2 positive cell line. In keeping with that classification, molecular profiling of this line resulted in it being classified as a HER2 amplified cell line. 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: The Oncogene Signature below is indicative of strong and essential signaling through the PI3’K-AKT pathway. As mentioned above, not only is ERBB2 overexpressed and essential in this cell line, which is a strong driver of PI3’K-AKT signaling, there is also an activating mutation in the PIK3CA oncogene and an inactivating mutation in PTEN! There is also a point mutation in VHL and this gene was a hit in the CRISPR screen, and ATP6AP1 is amplified, overexpressed and was essential in the CRISPR screen. Thus, this cell line has a number of unique molecular features to go along with its highly unusual metastatic site.
| Gene | CRISPR score | Demeter score | Log fold change | DNA amp | mutation | occ. In Cosmic |
| ERBB2 | -1.532579796 | -0.02423158 | 2.298230297 | 1.2681 | ||
| VHL | -1.478211774 | -0.092164211 | -0.171520636 | -0.0655 | p.L89L | 7 |
| PIK3CA | -1.17563853 | -1.197997 | -0.262086925 | 0.5131 | p.H1047R | 1582 |
| ATP6AP1 | -0.729281235 | -0.198378605 | 1.747802926 | 1.213 | ||
| ELF3 | -0.207460446 | -0.053541121 | -1.286613645 | 1.0616 | ||
| PAX5 | -0.023616343 | -0.061846218 | 0.020775394 | 0.5678 | p.S269L | 23 |
| GNA13 | 0.158906912 | 0.185566464 | 1.371835512 | 1.191 | ||
| PTEN | 0.827787439 | 0.093232657 | -0.009863611 | -0.082 | p.E307K | 35 |
MDA-MB-453 drug sensitivities. The oncogene signature shows that this cell line has two functional druggable oncogenes, and indeed the Tier 1 list of drugs shows that the cells are sensitive to inhibitors of both the activated oncogenes. Beyond that, this cell line presents with many druggable targets, some of which were found to be essential in the screen and thus appear in Tier 2, and a plethora of sensitivities to pan-specific drugs to which the cells exhibit moderate to high sensitivity.
| MDA-453.T1 | |||||||||
| Drug name | Gene symbol_HGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit | ||
| Alpelisib | PIK3CA | 0 | -2.263952 | 0.5131 | -0.262086925 | p.H1047R | 1 | ||
| CP724714 | ERBB2 | -2.496664 | 0 | 1.2681 | 2.298230297 | p.L145L | 0 | ||
| MDA-453.T2 | |||||||||
| Drug name | Gene symbol_HGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit | achilles_score | demeter |
| JQ1 | BRD4 | -0.595323 | -2.690575 | -0.0812 | -0.04618357 | p.H740Y | 0 | -1.389935945 | -0.821481897 |
| Rapamycin | MTOR | 0 | -1.985899 | -0.1011 | 0.273103556 | NULL | 0 | -1.348313132 | -1.139765852 |
| OTX015 | BRD4 | 0 | -1.71702 | -0.0812 | -0.04618357 | p.H740Y | 0 | -1.389935945 | -0.821481897 |
| VE-822 | ATR | 0 | -1.711095 | -0.0852 | -0.113594666 | NULL | 0 | -0.96587385 | -0.351949058 |
| I-BET-762 | BRD4 | -1.411328 | -1.611555 | -0.0812 | -0.04618357 | p.H740Y | 0 | -1.389935945 | -0.821481897 |
| MDA-453.T3 | |||||||||
| Drug name | Gene SymbolHGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit | achilles_score | demeter |
| JQ1 | BRD2 | -0.595323 | -2.690575 | -0.0907 | 0.256453644 | NULL | 0 | -0.221724661 | -0.17330026 |
| JQ1 | BRD3 | -0.595323 | -2.690575 | -0.0831 | 0.212306065 | p.P525L | 0 | 0.075207925 | 0.147737795 |
| JQ1 | BRDT | -0.595323 | -2.690575 | -0.0632 | 0 | NULL | 0 | -0.002924225 | -0.114514524 |
| OF-1 | BRD1 | 0 | -2.475373 | 0.3702 | 0.966079287 | NULL | 0 | -0.235123451 | -0.174322823 |
| OF-1 | BRPF1 | 0 | -2.475373 | -0.0655 | 0.182338729 | NULL | 0 | -0.157499808 | 0.054778033 |
| XAV939 | TNKS | 0.816822 | -2.187768 | -1.1061 | -0.616222795 | NULL | 0 | -0.000669294 | 0.015152558 |
| XAV939 | TNKS2 | 0.816822 | -2.187768 | -0.082 | 0.067399155 | NULL | 0 | 0.14299426 | -0.133609697 |
| Ruxolitinib | JAK1 | 0.394871 | -2.046408 | -0.0632 | -1.314611956 | NULL | 0 | -0.034915396 | 0.122642404 |
| Ruxolitinib | JAK2 | 0.394871 | -2.046408 | -0.947 | -0.849091023 | NULL | 0 | 0.128545595 | 0.051318883 |
| MK-2206 | AKT1 | -0.173188 | -2.030301 | 0.4836 | 1.364101649 | NULL | 0 | -0.347159222 | -0.32908003 |
| MK-2206 | AKT2 | -0.173188 | -2.030301 | -0.2099 | -0.173800391 | NULL | 0 | -0.067704266 | -0.074750951 |
| GSK1904529A | IGF1R | -0.713257 | -1.869844 | -1.398 | -1.067931409 | NULL | 0 | 0.143835602 | -0.020499942 |
| GSK1904529A | INSR | -0.713257 | -1.869844 | -0.0497 | -1.020012751 | NULL | 0 | 0.053087776 | 0.092001503 |
| MN-64 | TNKS | 0 | -1.758468 | -1.1061 | -0.616222795 | NULL | 0 | -0.000669294 | 0.015152558 |
| MN-64 | TNKS2 | 0 | -1.758468 | -0.082 | 0.067399155 | NULL | 0 | 0.14299426 | -0.133609697 |
| OTX015 | BRD2 | 0 | -1.71702 | -0.0907 | 0.256453644 | NULL | 0 | -0.221724661 | -0.17330026 |
| OTX015 | BRD3 | 0 | -1.71702 | -0.0831 | 0.212306065 | p.P525L | 0 | 0.075207925 | 0.147737795 |
| LCL161 | BIRC3 | -0.110894 | -1.709293 | 0.4435 | -0.831809722 | NULL | 0 | 0.132898249 | -0.173950142 |
| LCL161 | XIAP | -0.110894 | -1.709293 | -0.2991 | -0.346446511 | NULL | 0 | -0.047774699 | -0.0817743 |
| Uprosertib | AKT1 | 0 | -1.613658 | 0.4836 | 1.364101649 | NULL | 0 | -0.347159222 | -0.32908003 |
| Uprosertib | AKT2 | 0 | -1.613658 | -0.2099 | -0.173800391 | NULL | 0 | -0.067704266 | -0.074750951 |
| Uprosertib | AKT3 | 0 | -1.613658 | 0.7284 | -1.615037336 | NULL | 0 | 0.111819412 | 0.092357495 |
| I-BET-762 | BRD2 | -1.411328 | -1.611555 | -0.0907 | 0.256453644 | NULL | 0 | -0.221724661 | -0.17330026 |
| I-BET-762 | BRD3 | -1.411328 | -1.611555 | -0.0831 | 0.212306065 | p.P525L | 0 | 0.075207925 | 0.147737795 |
| GSK690693 | AKT1 | -1.527299 | 0 | 0.4836 | 1.364101649 | NULL | 0 | -0.347159222 | -0.32908003 |
| GSK690693 | AKT2 | -1.527299 | 0 | -0.2099 | -0.173800391 | NULL | 0 | -0.067704266 | -0.074750951 |
| GSK690693 | AKT3 | -1.527299 | 0 | 0.7284 | -1.615037336 | NULL | 0 | 0.111819412 | 0.092357495 |
| Amuvatinib | FLT3 | -1.947629 | 0 | 0.6034 | 0.121990524 | NULL | 0 | -0.235273756 | 0.193092444 |
| AR-42 | HDAC1 | -1.511317 | 0 | -0.0612 | 0.05496396 | NULL | 0 | -0.066128539 | -0.006863414 |
| Belinostat | HDAC1 | -1.523533 | 0 | -0.0612 | 0.05496396 | NULL | 0 | -0.066128539 | -0.006863414 |
| Amuvatinib | KIT | -1.947629 | 0 | -0.4567 | -0.089965762 | NULL | 0 | -0.030081808 | 0.014091657 |
| OSI-930 | KIT | -1.655257 | 0 | -0.4567 | -0.089965762 | NULL | 0 | -0.030081808 | 0.014091657 |
| Amuvatinib | PDGFRA | -1.947629 | 0 | -0.4567 | -0.083255504 | NULL | 0 | -0.160262618 | -0.008399353 |
| EHT-1864 | RAC1 | -1.782795 | 0 | -0.0738 | -0.43664359 | NULL | 0 | -0.166105026 | 0.087682709 |
| EHT-1864 | RAC2 | -1.782795 | 0 | 0.4797 | -2.498632631 | NULL | 0 | -0.161323895 | 0 |
| EHT-1864 | RAC3 | -1.782795 | 0 | -0.1208 | 1.738009461 | NULL | 0 | -0.490674319 | -0.165807526 |
