The HCC1395 cell line was derived from the primary ductal carcinoma of a 40 year old Caucasian female. The cell line is ER and HER2 negative and has been classified as a Basal A triple negative cell line. The STR profile for this cell line, along with links to complete genomic information on these cells can be found at Cellosaurus, at the COSMIC web site, and at the DepMap portal.
Oncogene Signature:
Like most basal type breast cancer cell lines, this line has a TP53 mutation that results in overexpression of the gene at the mRNA level. Even though the gene is overexpressed, it did not hit as essential in either screen suggesting that it is still acting as a mutated tumor suppressor gene. The cells have three functional oncogenes characterized by low level gene amplification and overexpression, and one of these genes, SMG1 was a hit in both functional screens, while DICER1 and XRCC2 barely made the cut points for hits in the CRISPR screen but not the RNAi screen. Three other genes with low level amplifications are in the signature which did not hit in the screens, although RHEB was close to the cutpoint. As can be seen from the functional-druggable signature for this cell line, these cells are not sensitive to any of the BRAF targeted drugs, which is consistent with the lack of essentiality of BRAF in these cells. Contrast this situation with DU4475 cells with a BRAF mutation in which the gene is highly essential and the cells are highly drug sensitive.
| Gene | CRISPR score | Demeter score | Log fold change | DNA amp | mutation | occ. In Cosmic |
| SMG1 | -1.01877049 | -0.886562597 | 1.009418841 | 1.003392 | ||
| DICER1 | -0.697109798 | 0.029298858 | 1.027292633 | 1.080139 | ||
| XRCC2 | -0.563910363 | 0.065933136 | 1.538970721 | 1.450304 | ||
| RHEB | -0.337070067 | -0.419621069 | 1.89851863 | 1.179665 | ||
| BRAF | -0.130060288 | -0.041343842 | 1.16790571 | 1.021689 | ||
| EZH2 | 0.261839538 | 0.03810737 | 1.741910422 | 1.179665 | ||
| TP53 | 0.284548317 | -0.272936121 | 1.90466336 | 0.091694 | p.R175H | 980 |
HCC1395 Drug Sensitivities: This Basal A triple negative breast cancer cell line, despite not exhibiting any functional-druggable oncogenes, does present with some interesting drug sensitivities. Note that in Tier 1, we find that the MET oncogene was slightly amplified but not overexpressed. And, because this gene is not overexpressed, nor was it a hit in the functional screen, this gene did not make the oncogene signature. Nevertheless, the cells do exhibit moderate sensitivity to the MET targeted drug SU11274. Tier 2 shows drug sensitivities more typical for basal breast cancers as there are two druggable targets that were hits in the screen and show good sensitivity to the drugs. Finally, Tier 3 shows that the cells actually exhibit moderate sensitivity to several drugs that target multiple signaling molecules, which suggests that there is significant inhittable signaling pathways operative in these cells.
| HCC1395.T1 | |||||||||
| Drug name | Gene symbol_HGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit | ||
| SU11274 | MET | -1.616133 | 0 | 1.338879 | 0.898640674 | NULL | 0 | ||
| HCC1395.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 | -1.783444 | -0.425382 | -0.13410964 | NULL | 0 | -0.58015435 | -0.235991235 |
| MK-8776 | CHEK1 | 0 | -1.783444 | -0.426651 | 0.46302137 | NULL | 0 | -2.443452813 | -0.553491595 |
| AZD7762 | CHEK1 | -0.159823 | -1.673471 | -0.426651 | 0.46302137 | NULL | 0 | -2.443452813 | -0.553491595 |
| HCC1395.T3 | |||||||||
| Drug name | Gene SymbolHGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit | achilles_score | demeter |
| MK-8776 | CHEK2 | 0 | -1.783444 | 0.808053 | 0.733587991 | NULL | 0 | 0.211821707 | 0.024826715 |
| AZD7762 | CHEK2 | -0.159823 | -1.673471 | 0.808053 | 0.733587991 | NULL | 0 | 0.211821707 | 0.024826715 |
| PD173074 | FGFR1 | -0.883259 | -1.647232 | -0.419478 | 0.538209792 | p.S36L | 0 | -0.352628878 | -0.148838994 |
| PD173074 | FGFR3 | -0.883259 | -1.647232 | -1.3041 | -1.54863887 | NULL | 0 | -0.130044469 | -0.05346922 |
| AZD4547 | FGFR1 | 0 | -1.548069 | -0.419478 | 0.538209792 | p.S36L | 0 | -0.352628878 | -0.148838994 |
| AZD4547 | FGFR2 | 0 | -1.548069 | 0.479983 | 1.207527507 | NULL | 0 | 0.093610511 | -0.167370961 |
| AZD4547 | FGFR3 | 0 | -1.548069 | -1.3041 | -1.54863887 | NULL | 0 | -0.130044469 | -0.05346922 |
| Pazopanib | CSF1R | -1.748607 | 0 | 0.200212 | 0.049668808 | p.Y61Y | 0 | -0.207205807 | 0.067550428 |
| CHIR-99021 | GSK3A | -2.006764 | 0 | -0.434119 | -0.34046343 | NULL | 0 | -0.046188774 | -0.052016869 |
| CHIR-99021 | GSK3B | -2.006764 | 0 | -0.390792 | -0.00316862 | NULL | 0 | 0.047247304 | 0.065358202 |
| Pazopanib | KIT | -1.748607 | 0 | -0.277039 | -0.04773753 | NULL | 0 | -0.248164883 | 0.148700771 |
| Pazopanib | PDGFRB | -1.748607 | 0 | 0.200212 | 0.154509949 | p.T882I | 0 | -0.013960925 | 0.038195991 |
