The CAL120 breast cancer cell line was derived from the pleural effusion metastasis of a 43 year old Caucasian female previously diagnosed with breast carcinoma. The cell line is ER and HER2 negative and has been classified as a Basal B cell line. The STR profile along with a description of the genomic features of this cell line can be found at Cellosaurus, at COSMIC, or at DepMap portal.
Oncogene Signature:
There are several interesting features of the Oncogene Signature of this cell line. First, the CDK4 oncogene is amplified, overexpressed, and was a strong hit in the RNAi screen making this a functional driving oncogene in this cell line. Indeed, this gene is considered to be strongly selective when it is a hit in the RNAi screen, so the Demeter score this gene shows it to be a true driving oncogene for these cells. These cells, like most basal breast cancer cell lines have a TP53 mutations in this case resulting in significant loss of TP53 expression at the mRNA level. It is also clear from this signature that genes from the 8p11.p12 genomic region are amplified and overexpressed in these cells, including FGFR1, KATA6A, and NSD3. This is of interest for several reasons. First, this region of gene amplification has been strongly associated with aggressive luminal breast cancers, and yet this cell line is a Basal B line. Second, while FGFR1, NSD3 and KAT6A have all been implicated as driving oncogenes when amplified and overexpressed, none of these amplicon genes were hits in the RNAi screen. Thus, the functional significance of this amplicon in this context is unclear.
| Gene | CRISPR score | Demeter score | Log fold change | DNA amp | mutation | occ. In Cosmic |
| CDK4 | -1.064651038 | 3.074435932 | 3.1863 | |||
| TP53 | -0.23162552 | -1.369282019 | -0.1894 | NA | 34 | |
| FGFR1 | -0.180513511 | 3.670521079 | 2.0492 | |||
| KAT6A | -0.091665719 | 1.431275283 | 1.44 | |||
| YES1 | -0.033623526 | 1.271268113 | 1.0396 | |||
| IL7R | -0.031647418 | 3.356158059 | 1.0578 | |||
| MDM2 | 0.13346281 | 1.452140159 | 1.8654 | |||
| NSD3 | 0.13589207 | 1.975544106 | 2.0492 | |||
| RRAS | 0.14265357 | 3.939625082 | 2.0862 | |||
| ARHGEF28 | 0.177157726 | 3.348531868 | 1.0929 |
CAL120 drug sensitivities. The first thing that one notices when looking at the drug sensitivities for this cell line is that there are no Tier 1 targeted drugs. This seems odd since, as indicated above, CDK4 is a true driving oncogene for this cell line. And yet, if one consults the Functional Druggable signature for this cell line, it can be seen that these cells are actually resistant to CDK4 targeted drugs. So, this oncogene is quite different from ERBB2 or PIK3CA in that a genomic alteration in this gene is not associated with drug sensitivity. Beyond that, there is an interesting Tier 2 drug as the BCL2 oncogene, despite not being amplified, was a strong screen hit and the cells are highly sensitive to the BCL2L1 specific drug WEHI-539. ROCK1 targeted drugs appear in Tier3, and indeed, a second ROCK1 targeted drug had a Z-score of -1.4 putting it just below the cut-point for this drug sensitivity. That said, this shows that the cells are actually quite sensitivity to two different ROCK targeted drugs suggesting strongly that these sensitivities reflect actual essentialness of one or both of the ROCK genes.
| CAL120.Tier1 | ||||||||
| None | ||||||||
| CAL120.Tier2 | ||||||||
| Drug name | symbol_HGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | mutation | lfc | achilles_score | demeter |
| WEHI-539 | BCL2L1 | 0 | -2.264125 | 0.5655 | NULL | 1.33501893 | NULL | -1.208544341 |
| CAL120.Tier3 | ||||||||
| Drug name | Gene SymbolHGNC | z_score_GDSC1 | z_score_GDSC2 | DNA_amp | lfc | mutation | achilles_score | demeter |
| GSK429286A | ROCK1 | -1.652062 | 0 | -0.3152 | -0.31852677 | NULL | NULL | 0.35694235 |
| GSK429286A | ROCK2 | -1.652062 | 0 | -0.2527 | -0.12150058 | NULL | NULL | 0.031724183 |
