The MDA-MB-415 breast cancer cell line

The MDA-MB-415 breast cancer cell line is an ER-positive, HER2 negative  breast cancer cell line derived from the pleural effusion metastasis of a 38 year old Caucasian female previously diagnosed with breast adenocarcinoma.   By molecular profiling, this cell line has been classified as a HER2 amplified cell line, even though the HER2 gene is not amplified in these cells.  The STR profile along with other genomic data and information pertinent to this cell line can be found here at Cellosaurus, or here at COSMIC, or here at DepMap portal.

Oncogene Signature: This Oncogene Signature bears several interesting features that are relevant to the aggressiveness of this ER-positive breast cancer cell line.  First, as can be seen, the ER-alpha is highly overexpressed in the cells and the gene scored as a hit in both functional screens indicating that the ER is essential in this cell line.  The ESR1 overexpression is accompanied by a PTEN mutation, indicative of PIK3’K-AKT signaling in these cells, and this is occurring in the context of a TP53 mutation.   Finally, as is relatively common in aggressive ER positive breast cancer cells, these cells have an amplification and overexpression of CCND1 (cyclinD1) and this gene was also found to be essential in both screens in this cell line.

Gene CRISPR score Demeter score Log fold change DNA amp mutation occ. In Cosmic
ESR1 -1.169421071 -0.512938733 2.102237023 0.340575
CCND1 -1.704585324 -0.558654284 1.171031271 3.204665
TP53 0.016179278 -0.260718914 0.014355648 -0.076872 p.Y236C 94
MAP2K4 0.094058185 0.074221772 -1.160098575 -0.076872 p.S280* 9
PTEN 0.401407618 0.04562247 -0.456359869 -0.617562 p.C136Y 51

Drug sensitivities of MDA-MB-415.  The oncogene signature shows that this cell line is ER+ in the context of PTEN and TP53 mutations.  As a result of these genomic alterations, the cells are quite sensitive to ER-targeted drugs, to PI3’K targeted drugs, and to AKT targeted drugs, indicating the importance of this pathway in the context of the PTEN alteration.  The cells also overexpress a mutant form of the KIT oncogene and the cells exhibit sensitivity to drugs that target this gene.  KIT does not appear in the oncogene signature because it is overexpressed in the absence of gene amplification.

MDA-415.T1
Drug name Gene symbol_HGNC z_score_GDSC1 z_score_GDSC2 DNA_amp lfc mutation COSMIC_hit
Fulvestrant ESR1 0 -1.841631 0.340575 2.102237023 NULL 0
GDC0810 ESR1 0 -1.503542 0.340575 2.102237023 NULL 0
Amuvatinib KIT -1.704202 0 -0.097498 3.397754902 p.K626R 0
MDA-415.T2
Drug name Gene symbol_HGNC z_score_GDSC1 z_score_GDSC2 DNA_amp lfc mutation COSMIC_hit achilles_score demeter
AZD8186 PIK3CB 0 -3.920358 -0.065317 -0.656679813 NULL 0 -0.98761888 0.013500753
Ipatasertib AKT1 0 -2.951623 -0.028844 -0.009360516 NULL 0 -0.650956184 -0.610826945
Ipatasertib AKT2 0 -2.951623 0.143003 -0.467635545 NULL 0 -0.71427397 -0.169899205
AZD5363 AKT1 0 -2.489904 -0.028844 -0.009360516 NULL 0 -0.650956184 -0.610826945
AZD5363 AKT2 0 -2.489904 0.143003 -0.467635545 NULL 0 -0.71427397 -0.169899205
Afuresertib AKT1 0 -2.333152 -0.028844 -0.009360516 NULL 0 -0.650956184 -0.610826945
Afuresertib AKT2 0 -2.333152 0.143003 -0.467635545 NULL 0 -0.71427397 -0.169899205
Uprosertib AKT1 0 -2.157191 -0.028844 -0.009360516 NULL 0 -0.650956184 -0.610826945
Uprosertib AKT2 0 -2.157191 0.143003 -0.467635545 NULL 0 -0.71427397 -0.169899205
MK-2206 AKT1 -1.426608 -2.052637 -0.028844 -0.009360516 NULL 0 -0.650956184 -0.610826945
MK-2206 AKT2 -1.426608 -2.052637 0.143003 -0.467635545 NULL 0 -0.71427397 -0.169899205
AZD6482 PIK3CB -2.970335 -1.90366 -0.065317 -0.656679813 NULL 0 -0.98761888 0.013500753
AT13148 AKT1 0 -1.81894 -0.028844 -0.009360516 NULL 0 -0.650956184 -0.610826945
Rapamycin MTOR 0 -1.662719 -0.027734 0.320785701 NULL 0 -1.672703743 -1.18157649
Rapamycin MTOR 0 -1.662719 -0.027734 0.320785701 NULL 0 -1.672703743 -1.18157649
AKT inhibitor VIII AKT1 -1.814796 0 -0.028844 -0.009360516 NULL 0 -0.650956184 -0.610826945
AKT inhibitor VIII AKT2 -1.814796 0 0.143003 -0.467635545 NULL 0 -0.71427397 -0.169899205
MDA-415.T3
Drug name Gene SymbolHGNC z_score_GDSC1 z_score_GDSC2 DNA_amp lfc mutation COSMIC_hit achilles_score demeter
AZD8186 PIK3CA 0 -3.920358 0.635502 -0.476275427 NULL 0 -0.065050595 -0.451854236
AZD8186 PIK3CB 0 -3.920358 -0.065317 -0.656679813 NULL 0 -0.98761888 0.013500753
Ipatasertib AKT2 0 -2.951623 0.143003 -0.467635545 NULL 0 -0.71427397 -0.169899205
Ipatasertib AKT3 0 -2.951623 0.310037 -1.533353538 NULL 0 0.16809164 0.230146862
AZD5363 AKT2 0 -2.489904 0.143003 -0.467635545 NULL 0 -0.71427397 -0.169899205
AZD5363 AKT3 0 -2.489904 0.310037 -1.533353538 NULL 0 0.16809164 0.230146862
AZD5363 ROCK2 0 -2.489904 -0.62448 -1.364155903 NULL 0 -0.180079323 -0.108944232
Afuresertib AKT2 0 -2.333152 0.143003 -0.467635545 NULL 0 -0.71427397 -0.169899205
Afuresertib AKT3 0 -2.333152 0.310037 -1.533353538 NULL 0 0.16809164 0.230146862
Uprosertib AKT2 0 -2.157191 0.143003 -0.467635545 NULL 0 -0.71427397 -0.169899205
Uprosertib AKT3 0 -2.157191 0.310037 -1.533353538 NULL 0 0.16809164 0.230146862
MK-2206 AKT2 -1.426608 -2.052637 0.143003 -0.467635545 NULL 0 -0.71427397 -0.169899205
AZD6482 PIK3CB -2.970335 -1.90366 -0.065317 -0.656679813 NULL 0 -0.98761888 0.013500753
Fulvestrant ESR2 0 -1.841631 -0.028844 0.116460433 NULL 0 0.15360086 0.038762559
GDC0810 ESR2 0 -1.503542 -0.028844 0.116460433 NULL 0 0.15360086 0.038762559
AKT inhibitor VIII AKT2 -1.814796 0 0.143003 -0.467635545 NULL 0 -0.71427397 -0.169899205
AKT inhibitor VIII AKT3 -1.814796 0 0.310037 -1.533353538 NULL 0 0.16809164 0.230146862
Amuvatinib FLT3 -1.704202 0 -0.088205 -0.014213859 NULL 0 -0.282459148 0.150164938
Amuvatinib KIT -1.704202 0 -0.097498 3.397754902 p.K626R 0 -0.459307807 0.019685458
Amuvatinib PDGFRA -1.704202 0 -0.097498 -0.083255504 NULL 0 -0.254550712 0.169086726