The MDA-MB-134VI breast cancer cell line was derived from the pleural effusion metastasis of a 47 year old Caucasian female previously diagnosed with invasive lobular carcinoma. The cell line is ER-positive and HER2 negative and has been classified as a luminal breast cancer cell line. STR profiling data along with genomic data and other information pertinent to this cell line can be found here at Cellosaurus or here at DepMap portal. This is no COSMIC entry for this cell line.
Oncogene Signature: There are several interesting features of the Oncogene Signature for this cell line, and unfortunately, this line has not yet been screened in project Achilles either using their CRISPR or RNAi based approaches, so we do not know the essentiality associated with any of the genes listed below. Because we do know that there is a very strong association between ESR1 (ER-alpha) overexpression and essentiality, it is highly likely that this gene is essential in these cells as well, and this cell line was also not screened for drug sensitivity in the genomics of drug sensitivity in cancer database. This is particularly unfortunate because, as can be seen from the signature below, this cell line is an excellent model for breast cancers that harbor the 8p11-p12 region of gene amplification. Three putative oncogenes are part of this amplicon as shown below; FGFR1, NSD3, and KAT6A. Our laboratory has published extensively on the genomic functions of NSD3 and KAT6A in breast cancer cells bearing the amplicon. We have also published data that shows that FGFR1 is rarely a true driver oncogene when the amplicon is present. It is well known that FGFR1 and NSD3 are always co-amplified and overexpressed and KAT6A is sometimes, but not always part of the amplicon. The lack of essentiality and drug sensitivity data for this line is particularly unfortunate because if there is any cell line where FGFR1 could be a functional driver it is this one, because the gene is most highly amplified and overexpressed in these cells. Adding to the uncertainty associated with these cells, there is a discrepancy in the mutation profile for this gene in Expasy.org and DepMap. The Expasy.org page shows point mutations in CDH1, KRAS and TP53, in addition to the MAP2K4 mutation shown below. The CDH1 mutation is consistent with the original diagnosis of invasive lobular carcinoma. So, in that regard, these cells are very similar to the SUM-44 cell line that we developed which is also highly ER positive, harbors the 8p11 amplicon, has a CDH1 mutation and was derived from the pleural effusion metastasis of a patient previously diagnosed with invasive lobular carcinoma. We have shown that FGFR1 plays little or no role in the growth potential of SUM-44 cells, but there are some data in the literature suggestive of a role for FGFR1 in the MDA-MB-134 cells. Given that, it is unfortunate that there are so many holes in the data for this cell line. Data in the literature derived from this cell line has been used to justify the clinical trials performed in patients with FGFR1 gene amplification using FGFR targeted drugs, and these trials have been uniformly negative, which also suggests that FGFR1 is rarely a driver oncogene in cells with the 8p11-p12 amplicon.
| Gene | CRISPR score | Demeter score | Log fold change | DNA amp | mutation | occ. In Cosmic |
| ESR1 | 5.362032376 | 0.0513 | ||||
| FGFR1 | 6.240397364 | 2.8017 | ||||
| NSD3 | 3.21710149 | 2.8017 | ||||
| CCND1 | 3.248010371 | 2.7548 | ||||
| KAT6A | 2.775907908 | 2.5342 | ||||
| PAK1 | 4.069760933 | 2.5056 | ||||
| RPS6KB2 | 2.110966889 | 1.964 | ||||
| MDM4 | 2.063380327 | 1.0778 | ||||
| HDAC7 | 1.601055831 | 1.0003 | ||||
| MAP2K4 | -0.007976648 | -1.0082 | p.S184L | 10 |
Unfortunately, there are no drug sensitivity data for this cell line in either of the GDSC databases, nor was this cell included in either screen. This is unfortunate given that this cell line is the most likely to have a dependency on FGFR1 signaling.
