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

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
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

FVB-Tg(C3-1-TAg)cJeg Mammary gland carcinoma Mammary gland

observed

B6;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.Cg-Tg(WapMyc)212Bri 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

BALB/cJ-Trp53tm1Tyj/+ Mammary gland carcinoma
  • gamma-radiation
Mammary gland

observed

FVB/NJ Mammary gland normal tissue (control) Mammary gland

not applicable

C57BL/6 Mammary gland normal tissue (control) Mammary gland

not applicable