The HCC1143 human breast cancer cell line is an ER-negative, HER2 negative cell line that is classified as being a Basal A type of triple negative line. The cell line was derived from the primary ductal carcinoma of a 52 year old Caucasian female. The complete STR profile for this cell line along with links to other genomics resources pertinent to this cell line can be found at Cellosaurus, COSMIC, or DepMap portal.
Oncogene Signature*: The oncogene signature for this Basal A cell line is interesting and consistent with its triple negative, basal A lineage. The cells have amplifications on the MYC and CCND1 genes, both of which are overexpressed and were hits in the screen. BRD4 is also highly amplified and overexpressed in these cells and was a screen hit, and UBR5 is also slightly amplified and overexpressed and a screen hit. Thus, these cells have at least four functional-driving oncogenes. There are other interesting features of this oncogene signature including a high level amplification of the NOTCH3 gene which is also highly overexpressed. This gene was not a hit in either screen, and it’s possible that the this is a false negative result because of the very high amplification and overexpression levels.
| Gene | CRISPR score | Demeter score | Log fold change | DNA amp | mutation |
| MYC | -1.36307114 | -0.523539258 | 1.787474167 | 1.179693 | |
| CCND1 | -1.092521151 | -0.210310799 | 2.113837796 | 2.937997 | |
| UBR5 | -0.967788877 | -0.700455761 | 1.464138659 | 1.481055 | |
| BRD4 | -0.919886642 | -0.619033938 | 3.307053025 | 3.005586 | |
| AGO2 | -0.496523147 | -0.125265579 | 1.268449392 | 1.179693 | |
| SAMHD1 | -0.253477045 | 0.498921261 | 1.486863041 | 1.038046 | |
| MDM2 | -0.228512475 | 0.1260052 | 2.219520091 | 1.551261 | |
| DNMT3B | -0.156854086 | -0.085660264 | 2.08273945 | 1.766759 | |
| ASXL1 | 0.026798631 | -0.26994215 | 2.695951207 | 1.766759 | |
| MAFB | 0.246457428 | -0.173887789 | 1.831714887 | 1.038046 | |
| NOTCH3 | 0.479736261 | -0.088885152 | 4.462506945 | 3.005586 | |
| RECQL4 | -0.034252934 | 1.570378639 | 1.179693 | ||
| ICOSLG | 2.595804678 | 1.385713 |
* There is a bit of confusion regarding the genomic data for this cell line. The oncogene signature above was determined using our data base with data derived from DepMap portal. The DepMap portal page for this cell line, indicates that TP53 was a top essential gene and indeed, the data in our database shows that TP53 is overexpressed and is an esssential gene in this line, as the gene was a hit in both functional screens. The Cellosaurus page for this line indicates the presence of a TP53 mutation and the COSMIC page indicates the same mutation. However this mutation is not indicated in the DepMap page which we take to be an inadvertent omission. That the gene is overexpressed and essential suggests that the mutation data shown in Cellosaurus and COSMIC is correct.
HCC1143 Drug sensitivity: Given that this is a triple negative, basal A cell line, it is not surprising that there is only one Tier 1 drug sensitivity in this cell line. The BCL2L1 oncogene is amplified but not overexpressed, but the cells do exhibit moderate sensitivity to a BCL2L1-specific drug. Beyond that, the Tier 2 drug VE-822 that targets ATR is of interest because the gene was a hit in both screens and we have noted similar associations between essentiality and drug sensitivity for this gene in other triple negative breast cancer cell lines.
There is one interesting Tier 3 drug associated with this cell line and once again, we have observed this for several basal type breast cancer cell lines. WIKI4 targets both TKKS and TNKS2 both of which are expressed in these cells, and the cells were quite sensitive to this targeted drug in the GDSC2 data set. Thus, this is a potentially interesting target in this cell line, and other basal type cell lines that exhibit sensitivity to this drug. Finally, it is interesting that despite the high level amplification and overexpression of BRD4 in this cell line, the cells are actually resistant to all BRD4 targeted drugs.
| HCC1143.T1 | |||||||||
| Drug name | Gene symbol_HGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit | ||
| WEHI-539 | BCL2L1 | 0 | -1.518444 | 1.766759 | 0.83391237 | NULL | 0 | ||
| HCC1143.T2 | |||||||||
| Drug name | Gene symbol_HGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit | achilles_score | demeter |
| VE-822 | ATR | 0 | -1.918563 | 0.563121 | 1.09090363 | NULL | 0 | -0.898594617 | -0.55058923 |
| HCC1143.T3 | |||||||||
| Drug name | Gene symbol_HGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | COSMIC_hit | achilles_score | demeter |
| WIKI4 | TNKS | 0 | -1.78362 | -0.7936 | -0.02225749 | NULL | 0 | -0.070447142 | -0.36165278 |
| WIKI4 | TNKS2 | 0 | -1.78362 | -0.192249 | 0.08597126 | NULL | 0 | -0.074964005 | -0.16167108 |
