The BT20 breast cancer cell line was derived from the primary tumor of a 74 year old Caucasian patient diagnosed with breast ductal carcinoma. It is an ER and HER2 negative cell line and has been classified as a Basal Type A cell line. The STR profile along with other data and references pertinent to this cell line can be found here at Cellosaurus, or here at COSMIC, or here at DepMap portal.
Oncogene Signature:
There are several noteworthy features of the Oncogene Signature of this basal breast cancer cell line. First, the line is driven by two different point mutations in the PIK3CA oncogene which, like essentially all breast cancer cell lines with this mutation, was essential as determined in the RNAi screen. In addition, the TRIP13 oncogene was amplified, overexpressed and a screen hit in these cells. The EGFR gene is also amplified and overexpressed in this cell line, but here, as in essentially all breast cancer cell lines in which this gene is overexpressed, it was not a hit in the screen. Based on this, one would predict that these cells would not be sensitive to EGFR-targeted drugs, and indeed, they are not. These cells, like most basal breast cancer cell lines has a TP53 mutation. The cells have an amplification of both NRAS and CDH1, but neither of these genes were screen hits.
| Gene | CRISPR score | Demeter score | Log fold change | DNA amp | mutation | occ. In Cosmic |
| PIK3CA | -0.604229288 | 0.652638094 | 0.0202 | p.P539R, p.H1047R | 1582 | |
| TRIP13 | -0.518300269 | 1.080812636 | 1.0673 | |||
| PRDM1 | -0.314553534 | 1.83703647 | 1.044 | |||
| EGFR | -0.285293945 | 4.192557487 | 2.5634 | |||
| PLCG2 | -0.20929726 | 1.367064315 | 1.0545 | |||
| TP53 | -0.127691696 | 1.702166557 | 0.2696 | p.K132Q | 79 | |
| CTCF | -0.1236548 | 1.158493506 | 1.6263 | |||
| NRAS | -0.106052408 | 1.796917266 | 1.6199 | |||
| NOTCH2 | -0.100568999 | 1.359623262 | 1.6199 | |||
| CDH1 | -0.036010394 | 2.227001157 | 1.4986 | |||
| ZFHX3 | -0.029099062 | 1.697531878 | 1.2444 | |||
| DROSHA | -0.0049851 | 1.485288035 | 1.2695 | |||
| CBFB | 0.006316799 | 1.444238931 | 1.0428 | |||
| CSDE1 | 0.048906446 | 2.461919236 | 1.6199 | |||
| CDKN2C | 0.103189719 | 0.594354301 | -0.1973 | p.A72P | 8 | |
| FBXW7 | 0.135033149 | 1.529367268 | 1.3423 | |||
| RB1 | 0.163666115 | 0.990831026 | 0.2406 | p.I388S, p.P515L | 21 | |
| CD58 | 0.195952754 | 2.096204777 | 1.6199 | |||
| CMTR2 | 1.74480954 | 1.285 |
BT20 drug sensitivity. As can be seen from the Oncogene Signature of this cell line, BT20 cells have two druggable oncogenes, PIK3CA and EGFR. In the case of PIK3A, this gene was a hit in the screen, and thus it is not surprising that the cells exhibit good sensitivity to the Class I alpha specific PI3’Kinase inhibitor Alpelisib. These cells also have an EGFR amplification associated with high level overexpression, however, EGFR was not a screen hit, and indeed, this gene is rarely a screen hit in breast cancer regardless of it’s amplification and expression status. In that regard, it is very interesting that these cells are quite sensitive to the EGFR monoclonal antibody drug Cetuximab, but do not exhibit significant sensitivity to either erlotinib or gefitinib. As can be seen on the page for MDA-468 cells, the same pattern of drug sensitivity/resistance is true for this EGFR amplified cell line. Given that the first and perhaps best drug that targets ERBB2 is also a monoclonal antibody based drug, perhaps this is telling us something mechanistically about how antibody drugs out perform small molecule kinase inhibitors for amplified growth factor receptors (?). Finally, there are no Tier 2 or Tier 3 drugs associated with this cell line.
| BT20. T1 | |||||||
| Drug name | Gene symbol_HGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit |
| Alpelisib | PIK3CA | 0 | -1.735854 | 0.0202 | 0.652638094 | p.P539R, p.H1047R | 1 |
| Cetuximab | EGFR | -1.714829 | 0 | 2.5634 | 4.192557487 | NULL | 0 |
