Reference SummaryPfefferle AD, Genome Biol 2013;14(11):R125
Title |
Transcriptomic classification of genetically engineered mouse models of breast cancer identifies human subtype counterparts. |
Authors |
Pfefferle AD; Herschkowitz JI; Usary J; Harrell JC; Spike BT; Adams JR; Torres-Arzayus MI; Brown M; Egan SE; Wahl GM; Rosen JM; Perou CM |
Journal |
Genome Biol |
Volume |
14 |
Issue |
11 |
Year |
2013 |
Pages |
R125 |
Abstract |
BACKGROUND: Human breast cancer is a heterogeneous disease consisting of multiple molecular subtypes. Genetically engineered mouse models are a useful resource for studying mammary cancers in vivo under genetically controlled and immune competent conditions. Identifying murine models with conserved human tumor features will facilitate etiology determinations, highlight the effects of mutations on pathway activation, and should improve preclinical drug testing. RESULTS: Transcriptomic profiles of 27 murine models of mammary carcinoma and normal mammary tissue were determined using gene expression microarrays. Hierarchical clustering analysis identified 17 distinct murine subtypes. Cross-species analyses using three independent human breast cancer datasets identified eight murine classes that resemble specific human breast cancer subtypes. Multiple models were associated with human basal-like tumors including TgC3(1)-Tag, TgWAP-Myc and Trp53-/-. Interestingly, the TgWAPCre-Etv6 model mimicked the HER2-enriched subtype, a group of human tumors without a murine counterpart in previous comparative studies. Gene signature analysis identified hundreds of commonly expressed pathway signatures between linked mouse and human subtypes, highlighting potentially common genetic drivers of tumorigenesis. CONCLUSIONS: This study of murine models of breast carcinoma encompasses the largest comprehensive genomic dataset to date to identify human-to-mouse disease subtype counterparts. Our approach illustrates the value of comparisons between species to identify murine models that faithfully mimic the human condition and indicates that multiple genetically engineered mouse models are needed to represent the diversity of human breast cancers. The reported trans-species associations should guide model selection during preclinical study design to ensure appropriate representatives of human disease subtypes are used. |
Links |
J:227323 – MGI References 24220145 – National Library of Medicine/PubMed |
| Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
|---|---|---|---|---|---|
| [not specified]-Rb1tm2Brn Rbl1tm1Tyj Tg(MMTV-cre)#Tfln | Mammary gland adenocarcinoma - cystic | Mammary gland |
observed |
||
| [not specified]-Rb1tm2Brn Rbl1tm1Tyj Tg(MMTV-cre)#Tfln | Mammary gland adenocarcinoma - poorly differentiated | Mammary gland |
observed |
||
| [not specified]-Rb1tm2Brn Rbl1tm1Tyj Tg(MMTV-cre)#Tfln | Mammary gland adenocarcinoma - solid | Mammary gland |
observed |
||
| [not specified]-Rb1tm2Brn Rbl1tm1Tyj Tg(MMTV-cre)#Tfln | Mammary gland adenocarcinoma - solid/nodular | Mammary gland |
observed |
||
| [not specified]-Rb1tm2Brn Rbl1tm1Tyj/+ Tg(MMTV-cre)#Tfln | Mammary gland adenocarcinoma - squamous | Mammary gland |
observed |
||
| STOCK Smarca4tm1Mag/+ | Mammary gland adenocarcinoma - trabecular | Mammary gland |
1.2 |
||
| STOCK Smarca4tm1Mag/+ | Mammary gland adenocarcinoma - trabecular/papillary | Mammary gland |
2.2 - 2.4 |
||
| [not specified]-Rb1tm2Brn Rbl1tm1Tyj Tg(MMTV-cre)#Tfln | Mammary gland adenomyoepithelioma - papillary | Mammary gland |
observed |
||
| FVB/N-Tg(MMTV-LPAR1)#Gbm | Mammary gland carcinoma | Mammary gland |
32 |
||
| FVB/N-Tg(MMTV-LPAR2)#Gbm | Mammary gland carcinoma | Mammary gland |
52.8 |
||
| FVB/N-Tg(MMTV-LPAR3)#Gbm | Mammary gland carcinoma | Mammary gland |
42.3 |
||
| FVB/N-Tg(MMTV-ENPP2)#Gbm | Mammary gland carcinoma | Mammary gland |
50 |
||
| BALB/cJ-Brca1tm1Bhk/+ Trp53tm1Tyj/+ | Mammary gland carcinoma |
|
Mammary gland |
observed |
|
| BALB/cJ-Trp53tm1Tyj/+ | Mammary gland carcinoma |
|
Mammary gland |
observed |
|
| C.Cg-Tg(WAPT121)66Tvd | Mammary gland carcinoma | Mammary gland |
observed |
||
| B6D2-Tg(WAPT121)66Tvd | Mammary gland carcinoma | Mammary gland |
observed |
||
| C57BL/6J-Tg(WapTAg)1Knw | Mammary gland carcinoma | Mammary gland |
observed |
||
| C57BL/6-Brca1tm2Cxd Trp53tm1Brd/+ Tg(MMTV-cre)4Mam | Mammary gland carcinoma | Mammary gland |
observed |
||
| FVB | Mammary gland carcinoma |
|
Mammary gland |
observed |
|
| FVB-Tg(C3-1-TAg)cJeg | Mammary gland carcinoma | Mammary gland |
observed |
||
| FVB-Tg(MMTVneu)202Mul | Mammary gland carcinoma | Mammary gland |
observed |
||
| FVB-Tg(MMTV-PyVT)634Mul | Mammary gland carcinoma | Mammary gland |
observed |
||
| FVB.Cg-Tg(Wnt1)1Hev | Mammary gland carcinoma | Mammary gland |
observed |
||
| FVB-Tg(WapNotch4)10Rnc | Mammary gland carcinoma | Mammary gland |
observed |
||
| FVB.Cg-Tg(WapMyc)212Bri | Mammary gland carcinoma | Mammary gland |
observed |
||
| C.129(B6)-Cdkn2ctm1Yxi | Mammary gland carcinoma | Mammary gland |
observed |
||
| FVB-Gt(ROSA)26Sortm1(Pik3ca*H1047R)Egan Tg(MMTV-cre)# | Mammary gland carcinoma | Mammary gland |
observed |
||
| [not specified]-Rb1tm2Brn Tg(MMTV-cre)#Tfln | Mammary gland carcinoma | Mammary gland |
observed |
||
| B6.129-Stat1tm1Rds | Mammary gland carcinoma | Mammary gland |
observed |
||
| FVB/NTac-Tg(MMTV-NCOA3)#Mybr | Mammary gland carcinoma | Mammary gland |
observed |
||
| FVB/N-Tg(MMTV-Fgf3)#Mul | Mammary gland carcinoma | Mammary gland |
observed |
||
| FVB.Cg-Tg(MMTV-vHaras)SH1Led | Mammary gland carcinoma | Mammary gland |
observed |
||
| FVB.Cg-Tg(MMTV-Myc)141-3Led | Mammary gland carcinoma | Mammary gland |
observed |
||
| B6;FVB-Tg(C3-1-TAg)cJeg | Mammary gland carcinoma | Mammary gland |
observed |
||
| B6D2-Tg(WAPT121)66Tvd Trp53tm1Tyj/+ | Mammary gland carcinoma | Mammary gland |
observed |
||
| BALB/cJ-Trp53tm1Tyj | Mammary gland carcinoma | Mammary gland |
observed |
||
| [not specified]-Rb1tm2Brn Rbl1tm1Tyj/+ Tg(MMTV-cre)#Tfln | Mammary gland carcinoma - acinar | Mammary gland |
observed |
||
| [not specified]-Rb1tm2Brn Rbl1tm1Tyj/+ Tg(MMTV-cre)#Tfln | Mammary gland carcinoma - adenosquamous | Mammary gland |
observed |
||
| STOCK Smarca4tm1Mag/+ | Mammary gland carcinoma - small cuboidal | Mammary gland |
1.2 |
||
| STOCK Smarca4tm1Mag/+ | Mammary gland carcinoma - trabecular | Mammary gland |
1.2 |
||
| STOCK Smarca4tm1Mag/+ | Mammary gland carcinoma - well-differentiated | Mammary gland |
1.2 |
||
| [not specified]-Rb1tm2Brn Rbl1tm1Tyj/+ Tg(MMTV-cre)#Tfln | Mammary gland keratoacanthoma - squamous | Mammary gland |
observed |
||
| STOCK Smarca4tm1Mag/+ | Mammary gland metaplasia - squamous | Mammary gland |
4.7 |
||
| BALB/cJ | Mammary gland normal tissue (control) | Mammary gland |
not applicable |
||
| FVB/NJ | Mammary gland normal tissue (control) | Mammary gland |
not applicable |
||
| C57BL/6 | Mammary gland normal tissue (control) | Mammary gland |
not applicable |
||
| [not specified]-Etv6tm3(NTRK3)Sho/+ Tg(Wap-cre)11738Mam | Mammary gland tumor | Mammary gland |
100 |
||
| [not specified]-Etv6tm3(NTRK3)Sho/+ Gt(ROSA)26Sortm1Sho Tg(Wap-cre)11738Mam | Mammary gland tumor | Mammary gland |
observed |
||
| FVB-Tg(C3-1-TAg)cJeg | Mammary gland tumor | Mammary gland |
observed |
||
| FVB-Tg(MMTVneu)202Mul | Mammary gland tumor | Mammary gland |
observed |
||
| FVB-Tg(MMTV-Fgfr2)#Jmr Tg(Wnt1)1Hev | Mammary gland tumor | Mammary gland |
observed |
||
| FVB-Tg(C3-1-TAg)cJeg | Mammary gland tumor - basal-like | Mammary gland |
observed |
||
| B6;FVB-Tg(C3-1-TAg)cJeg | Mammary gland tumor - basal-like | Mammary gland |
observed |
||
| FVB-Tg(MMTV-Erbb2)NK1Mul | Mammary gland tumor - luminal | Mammary gland |
observed |
||
| FVB-Tg(MMTV-Fgfr1)4775Jmr Tg(Wnt1)1Hev | Mammary gland tumor - solid |
|
Mammary gland |
100 |
|
| FVB-Tg(Wnt1)1Hev | Mammary gland tumor - type P |
|
Mammary gland |
52 |