The HCC202 Breast Cancer Cell Line

The HCC202 human breast cancer cell line was derived from a primary breast ductal carcinoma of an 82 year old Caucasian female.  The cell line is an ER-negative, HER2 positive line that exhibits and amplification and overexpression of HER2 (ERBB2).  It also is classified as a HER2 amplification subtype based on its expression profile.  The STR profile and all genomic information on these cells can be found at Cellosaurus, or at COSMIC, or at DepMap Portal.

Oncogene Signature:

The Oncogene Signature of this cell line is pretty straight forward and is consistent with the lineage characteristics of these cells.  The ERBB2 (HER2) oncogene is amplified, overexpressed, and the gene was a hit in both the CRISPR and RNAi functional screens.  Thus, HER2 is a clear driving oncogene in this cell line.  The cells also have a TP53 point mutation resulting in the almost complete loss of expression of this gene at the message level.  Beyond these two clear drivers, there are some other potentially interesting candidate oncogenes that are amplified and overexpressed in these cells, but only CDK12 came close to being a hit in the functional screens.

Gene CRISPR score Demeter score Log fold change DNA amp mutation occ. In Cosmic
ERBB2 -1.2242987 -0.528996056 5.288860045 3.263
CDK12 -0.21976893 -0.242533461 2.317290782 2.6486
TP53 -0.169223956 -0.334040952 -2.864383907 -0.5612 p.T284fs 25
KDM5C -0.093546277 -0.276182306 3.354434143 3.1631
NF1 -0.078245315 0.069159026 -1.20411873 -0.5118 NA 9
PDGFB -0.028176101 2.535255511 1.1381
SMC1A 0.053863415 -0.079703105 3.718372043 2.8798
HOXB13 0.263745493 0.053087432 4.515093281 2.8033
SPOP 0.314442401 0.026991263 1.57313777 1.8541
ICOSLG 1.751783085 1.0513

HCC202 drug sensitivities.  This ERBB2 amplified cell line seems to only be sensitive to ERBB2/HER2 targeted drugs and nothing else.  It also should be noted that there are only reported sensitivity data for 14 drugs in the GDSC2 data set, which may explain the paucity of drug sensitivity data for this cell line.  There are additional pan-ERBB specific targeted drugs to which the cells are sensitive that appear in Tier 3.  Also in Tier 3 are two drugs that have in common BTK as a target to which the cells are sensitive at least in the GDSC1 data set.

HCC202:T1
Drug name Gene symbol_HGNC z_score_GDSC1 z_score_GDSC2 DNA_amp lfc mutation COSMIC_hit
CI-1033 ERBB2 -1.880709 0 3.263 5.288860045 NULL 0
HCC202:T2
None
HCC202:T3
Drug name Gene SymbolHGNC z_score_GDSC1 z_score_GDSC2 DNA_amp lfc mutation achilles_score demeter
QL-XII-47 BMX -1.573564 0 -0.1047 0 NULL 0.109014447 -0.173033867
LFM-A13 BTK -2.136724 0 -1.4904 0 NULL -0.209648547 -0.140168442
QL-XII-47 BTK -1.573564 0 -1.4904 0 NULL -0.209648547 -0.140168442
CI-1033 EGFR -1.880709 0 0.4915 -0.257281546 NULL 0.209937922 0.087276944
AST-1306 EGFR -2.120082 0 0.4915 -0.257281546 NULL 0.209937922 0.087276944
CI-1033 ERBB4 -1.880709 0 -0.513 0.646740438 NULL 0.229862425 0.167131386
AST-1306 ERBB4 -2.120082 0 -0.513 0.646740438 NULL 0.229862425 0.167131386