The MDA-MB-361 breast cancer cell line is and ER-positive and HER2 positive breast cancer cell line derived from a brain metastasis of a 40 year old Caucasian female previously diagnosed breast adenocarcinoma. By molecular profiling, this cell line has also been classified as a HER2 amplified type breast cancer. 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: This is an exceptionally interesting cell line for several reasons. First it is one of the rare breast cancer cell lines derived from a brain metastasis, and like many such breast cancers, this one harbors an HER2 amplification with overexpression and the gene was a hit in the functional screen. In addition, the cells are ER-positive and highly overexpress the gene at the mRNA level, and here too, the gene was a hit in the shRNA screen. Finally, the cells have a PIK3CA mutation and this gene too was found to be highly essential in the functional screen. Thus, one might actually consider this cell line to be a Triple Positive breast cancer cell line. Beyond these oncogenic features, the cells harbor a TP53 mutation, and an NF1 mutation. Thus, two key tumor suppressor genes are also genomically altered in these cells. It is also quite remarkable that this cell line harbors the classic V600E point mutation in the BRAF oncogene and surprisingly, this gene was not a screen hit! Thus, this is a fascinating cell line and based on this signature, it is not difficult to see why it is so aggressive and resulted in a brain metastasis.
| Gene | CRISPR score | Demeter score | Log fold change | DNA amp | mutation | occ. In Cosmic |
| ESR1 | -0.583395334 | 3.039952745 | 0.1876 | |||
| PIK3CA | -1.284109778 | -0.64251067 | 0.1533 | p.E545K, p.K567R | 5 | |
| ERBB2 | -0.53421204 | 3.902117358 | 2.5961 | |||
| RAD51C | -0.379062245 | 1.94165134 | 2.061 | |||
| TP53 | -0.195223034 | -1.626394631 | -0.3319 | p.E56* | 27 | |
| CDK12 | -0.123319524 | 1.291995706 | 2.5961 | |||
| H3F3B | -0.091067007 | 2.241210623 | 1.4114 | |||
| BRIP1 | -0.061965077 | 1.466586541 | 1.7692 | |||
| GNA13 | 0 | 1.891754008 | 2.1491 | |||
| CDKN2A | 0.004892089 | -0.568529761 | -1.4347 | p.E18*, p.M52I | 1480 | |
| SOX9 | 0.026745124 | 1.212003766 | 1.4253 | |||
| BRAF | 0.03967665 | 0.275965456 | 0.1631 | p.V600E | 15808 | |
| PIK3C2G | 0.076226858 | 2.101744927 | 1.1335 | |||
| RNF43 | 0.088252797 | 2.688986293 | 1.5979 | |||
| SRSF2 | 0.134198278 | 1.276117722 | 1.489 | |||
| PRKAR1A | 0.146038231 | 1.161166241 | 1.4253 | |||
| NF1 | 0.167355862 | 0.397356509 | -0.3341 | p.K1290K | 12 | |
| PPM1D | 0.265285659 | 1.533549244 | 1.7692 |
MDA-MB-361 drug sensitivities. The Oncogene Signature of this cell line shows it to be an ER+ cell line with an ERBB2 amplification and a PIK3CA mutation. Interestingly, the Tier 1 drug list shows a drug that targets the ER and PIK3CA, but not ERBB2. Thus, this cell line is not particularly sensitive to ERBB2 specific drugs. With this in mind, it is interesting that both Tier 2 and Tier 3 show drugs that target one or more AKT family members to which the cells are quite sensitive. Finally, this is one of the few breast cancer cell line that show good sensitivity to an HDAC inhibitor.
| MDA-361.T1 | |||||||||
| Drug name | Gene symbol_HGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit | ||
| Fulvestrant | ESR1 | 0 | -1.5123 | 0.1876 | 3.039952745 | NULL | 0 | ||
| Alpelisib | PIK3CA | 0 | -2.538572 | 0.1533 | -0.64251067 | p.E545K, p.K567R | 1 | NULL | -1.284109778 |
| Pictilisib | PIK3CA | -1.363295 | -1.524887 | 0.1533 | -0.64251067 | p.E545K, p.K567R | 1 | NULL | -1.284109778 |
| MDA-361.T2 | |||||||||
| Drug name | Gene symbol_HGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit | achilles_score | demeter |
| MK-8776 | CDK2 | 0 | -1.936005 | 0.0355 | 0.328416789 | NULL | 0 | NULL | -0.551157072 |
| MK-8776 | CHEK1 | 0 | -1.936005 | -0.3753 | 0.061219698 | NULL | 0 | NULL | -0.577444821 |
| Fulvestrant | ESR1 | 0 | -1.5123 | 0.1876 | 3.039952745 | NULL | 0 | NULL | -0.583395334 |
| MK-2206 | AKT1 | -1.623234 | -1.071001 | -0.3873 | 0.83511099 | p.D3N | 0 | NULL | -0.724584829 |
| AKT inhibitor VIII | AKT1 | -2.91365 | 0 | -0.3873 | 0.83511099 | p.D3N | 0 | NULL | -0.724584829 |
| MDA-361.T3 | |||||||||
| Drug name | Gene SymbolHGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit | achilles_score | demeter |
| Entinostat | HDAC1 | 0 | -1.633136 | -0.3228 | 0.567036641 | NULL | 0 | NULL | -0.027384008 |
| Entinostat | HDAC3 | 0 | -1.633136 | -0.364 | 0.01502987 | NULL | 0 | NULL | -0.173597892 |
| MK-2206 | AKT2 | -1.623234 | -1.071001 | -0.5156 | 0.0580962 | NULL | 0 | NULL | -0.083030506 |
| AKT inhibitor VIII | AKT3 | -2.91365 | 0 | 0.156 | 1.397166804 | NULL | 0 | NULL | 0.147659783 |
| AKT inhibitor VIII | AKT2 | -2.91365 | 0 | -0.5156 | 0.0580962 | NULL | 0 | NULL | -0.083030506 |
