The JIMT1 breast cancer cell line was derived from the pleural effusion metastasis of a 62 old Caucasian female previously diagnosed with ductal carcinoma of the breast. The cell line is ER-negative and HER2 positive. This is an interesting cell line in some ways in that, according to Cellosaurus, this cell line does not have a HER2 amplification, however according to both COSMIC and DepMap portal, the cell line is HER2 amplified. To add to this inconsistency, based on expression profile, the cell line has been classified as belong to the Basal A subtype and not the classic HER2 subtype. Finally, there are papers in the literature in which this cell line has been used as a model for cells with a HER2 amplification but which are resistant to HER2 targeted drugs. Indeed, as can be seen using the Functional Druggable Signature tool, these cells are in fact resistant to HER2 targeted drugs, and this result in actually consistent with the data in the table below that shows that despite the amplification and overexpression of ERBB2 in these cells, the gene was not a hit in the CRISPR screen. All of this should be kept in mind when working with the JIMT1 cell line. The STR profile along with other genomic information pertinent to this cell line an be found here at Cellosaurus and here at COSMIC and here at DepMap portal.
Oncogene Signature: As can be seen below, these cells also have a PIK3CA mutation and the specific mutation reported here (from DepMap portal) is the same mutation noted in the Cellosaurus database. Furthermore, PIK3CA was a hit in the CRISPR screen, and this could be the reason that ERBB2 was not a screen hit and the cells are relatively resistant to HER2 targeted drugs. This would suggest that mutant PIK3CA and not amplified ERBB2 is the dominant driver of proliferation and survival in these cells. Finally, both AURKA and CDK4 were amplified and were hits in the CRISPR screen, making these three genes functional-driving oncogenes.
| Gene | CRISPR score | Demeter score | Log fold change | DNA amp | mutation | occ. In Cosmic |
| PIK3CA | -0.902268923 | 0.074417171 | 0.745165 | p.C420R | 40 | |
| AURKA | -0.890934515 | 1.400749991 | 1.206599 | |||
| CDK4 | -0.552838646 | 2.916204964 | 2.462638 | |||
| RRAS2 | -0.498957485 | 2.188000798 | 1.438283 | |||
| JUN | -0.423980167 | 3.313566652 | 1.701284 | |||
| ERBB2 | -0.312425716 | 2.716116958 | 2.836604 | |||
| CDK12 | -0.222996986 | 2.949550658 | 2.836604 | |||
| NCOA3 | -0.220494111 | 1.241033688 | 1.206599 | |||
| PTPN1 | -0.205123597 | 1.798675008 | 1.206599 | |||
| FGFR1 | -0.015140319 | 1.18454413 | 1.761785 | |||
| NSD3 | -0.001796642 | 1.992897673 | 1.761785 | |||
| TP53 | 0.025730579 | 1.581080839 | -0.335362 | p.R248W | 617 | |
| PIK3CB | 0.068406224 | 2.010981259 | 1.635365 |
JIMT1 drug sensitivity. As noted above, these cells, despite having an amplification with moderate overexpression of ERBB2 are not sensitive to any ERBB2 targeted drugs. Similarly, despite have a PIK3CA mutation, these cells are also not sensitive to any PI3’kinase inhibitors including Alpelisib! Thus, there are no Tier 1 drugs listed for this cell line. Tier 2 shows that that the cells are moderately sensitive to PLK1 and MTOR inhibitors, both of which were screen hits, and the same PLK inhibitor is shown in Tier 3 because it blocks multiple PLK family members that are expressed in these cells. One wonders if these cells, like the HCC1428 cells are just generally drug resistant.
| JIMT1.T1 | |||||||||
| None | |||||||||
| JIMT1.T2 | |||||||||
| Drug name | Gene symbol_HGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit | achilles_score | demeter |
| BI-2536 | PLK1 | 0 | -1.559118 | -0.307858 | 0.141421823 | NULL | 0 | -1.597057067 | NULL |
| Temsirolimus | MTOR | -1.784107 | 0 | -0.296549 | -0.4382062 | NULL | 0 | -1.298856256 | NULL |
| JIMT1.T3 | |||||||||
| BI-2536 | PLK2 | 0 | -1.559118 | -0.274756 | 1.682167281 | NULL | 0 | 0.002024863 | NULL |
| BI-2536 | PLK3 | 0 | -1.559118 | 0.27159 | 1.743533391 | NULL | 0 | -0.079651921 | NULL |
