RGD Reference Report - Identification of novel carcinogen-mediated mammary tumor susceptibility loci in the rat using the chromosome substitution technique. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Identification of novel carcinogen-mediated mammary tumor susceptibility loci in the rat using the chromosome substitution technique.

Authors: Adamovic, T  McAllister, D  Wang, T  Adamovic, D  Rowe, JJ  Moreno, C  Lazar, J  Jacob, HJ  Sugg, SL 
Citation: Adamovic T, et al., Genes Chromosomes Cancer. 2010 Nov;49(11):1035-45.
RGD ID: 4143380
Pubmed: PMID:20737482   (View Abstract at PubMed)
PMCID: PMC2943010   (View Article at PubMed Central)
DOI: DOI:10.1002/gcc.20812   (Journal Full-text)

We here report the genetic basis for susceptibility and resistance to carcinogen-mediated [7,12-dimethylbenz[a]anthracene (DMBA)] mammary tumorigenesis using the full panel of SS/BN consomic rat strains, in which substitutions of individual chromosomes from the resistant BN strain onto the genomic background of the susceptible SS strain were made. Analysis of 252 consomic females identified rat mammary Quantitative Trait Loci (QTLs) affecting tumor incidence on chromosomes 3 and 5, latency on chromosomes 3, 9, 14, and 19, and multiplicity on chromosomes 13, 16, and 19. In addition, we unexpectedly identified a novel QTL on chromosome 6 controlling a lethal toxic phenotype in response to DMBA. Upon further investigation with chromosomes 6 and 13 congenic lines, in which an additional 114 rats were investigated, we mapped (1) a novel mammary tumor QTL to a region of 27.1 Mbp in the distal part of RNO6, a region that is entirely separated from the toxicity phenotype, and (2) a novel and powerful mammary tumor susceptibility locus of 4.5 Mbp that mapped to the proximal q-arm of RNO13. Comparison of genetic strain differences using existing rat genome databases enabled us to further construct priority lists containing single breast cancer candidate genes within the defined QTLs, serving as potential functional variants for future testing. (c) 2010 Wiley-Liss, Inc.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Mcs25RatDrug-Related Side Effects and Adverse Reactions  IDA  RGD 
Mcs26RatExperimental Mammary Neoplasms  IDA DMBA inducedRGD 
Mcs27RatExperimental Mammary Neoplasms  IDA DMBA inducedRGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SS-Chr 3BN/McwiRatdecreased incidence of tumors by chemical induction inducedIAGP7,12-dimethyltetraphene (DMBA)compared to SS/JrHsdMcwiRGD 
SS-Chr 5BN/McwiRatdecreased incidence of tumors by chemical induction inducedIAGP7,12-dimethyltetraphene (DMBA)compared to SS/JrHsdMcwiRGD 
SS-Chr 3BN/McwiRatdecreased mammary gland tumor incidence inducedIAGP7,12-dimethyltetraphene (DMBA)compared to SS/JrHsdMcwiRGD 
SS-Chr 5BN/McwiRatdecreased mammary gland tumor incidence inducedIAGP7,12-dimethyltetraphene (DMBA)compared to SS/JrHsdMcwiRGD 
SS-Chr 6BN/McwiRatdecreased survivor rate inducedIAGP7,12-dimethyltetraphene (DMBA)compared to SS/JrHsdMcwiRGD 
SS.BN-(D6Rat149-D6Arb3)/McwiRatdecreased survivor rate inducedIAGP7,12-dimethyltetraphene (DMBA)compared to SS/JrHsdMcwiRGD 
SS.BN-(D6Rat149-D6Got171)/McwiRatdecreased survivor rate inducedIAGP7,12-dimethyltetraphene (DMBA)compared to SS/JrHsdMcwiRGD 
SS.BN-(D6Rat149-D6Rat18)/McwiRatdecreased survivor rate inducedIAGP7,12-dimethyltetraphene (DMBA)compared to SS/JrHsdMcwiRGD 
SS-Chr 14BN/McwiRatdecreased tumor latency inducedIAGP7,12-dimethyltetraphene (DMBA)compared to SS/JrHsdMcwiRGD 
SS-Chr 19BN/McwiRatdecreased tumor latency inducedIAGP7,12-dimethyltetraphene (DMBA)compared to SS/JrHsdMcwiRGD 
SS-Chr 9BN/McwiRatdecreased tumor latency inducedIAGP7,12-dimethyltetraphene (DMBA)compared to SS/JrHsdMcwiRGD 
SS.BN-(D13Hmgc64-RN34_13048990782)/McwiRatdecreased tumor latency inducedIAGP7,12-dimethyltetraphene (DMBA)compared to SS/JrHsdMcwiRGD 
SS.BN-(D6Rat119-D6Arb3)/McwiRatdecreased tumor latency inducedIAGP7,12-dimethyltetraphene (DMBA)compared to SS/JrHsdMcwiRGD 
SS.BN-(D6Rat119-D6Arb3)/McwiRatincreased incidence of tumors by chemical induction inducedIAGP7,12-dimethyltetraphene (DMBA)compared to SS/JrHsdMcwiRGD 
Mcs26Ratincreased mammary adenocarcinoma incidence  IDA DMBA inducedRGD 
Mcs27Ratincreased mammary adenocarcinoma incidence  IDA DMBA inducedRGD 
SS-Chr 13BN/McwiRatincreased mammary adenocarcinoma incidence inducedIAGP7,12-dimethyltetraphene (DMBA)compared to SS/JrHsdMcwiRGD 
SS-Chr 16BN/McwiRatincreased mammary adenocarcinoma incidence inducedIAGP7,12-dimethyltetraphene (DMBA)compared to SS/JrHsdMcwiRGD 
SS-Chr 19BN/McwiRatincreased mammary adenocarcinoma incidence inducedIAGP7,12-dimethyltetraphene (DMBA)compared to SS/JrHsdMcwiRGD 
SS.BN-(D13Hmgc64-RN34_13048990782)/McwiRatincreased mammary adenocarcinoma incidence inducedIAGP7,12-dimethyltetraphene (DMBA)compared to SS/JrHsdMcwiRGD 
SS.BN-(D6Rat119-D6Arb3)/McwiRatincreased mammary adenocarcinoma incidence inducedIAGP7,12-dimethyltetraphene (DMBA)compared to SS/JrHsdMcwiRGD 
SS-Chr 6BN/McwiRatincreased susceptibility to xenobiotic induced morbidity/mortality inducedIAGP7,12-dimethyltetraphene (DMBA)compared to SS/JrHsdMcwiRGD 
SS.BN-(D6Rat149-D6Arb3)/McwiRatincreased susceptibility to xenobiotic induced morbidity/mortality inducedIAGP7,12-dimethyltetraphene (DMBA)compared to SS/JrHsdMcwiRGD 
SS.BN-(D6Rat149-D6Got171)/McwiRatincreased susceptibility to xenobiotic induced morbidity/mortality inducedIAGP7,12-dimethyltetraphene (DMBA)compared to SS/JrHsdMcwiRGD 
SS.BN-(D6Rat149-D6Rat18)/McwiRatincreased susceptibility to xenobiotic induced morbidity/mortality inducedIAGP7,12-dimethyltetraphene (DMBA)compared to SS/JrHsdMcwiRGD 
SS-Chr 3BN/McwiRatincreased tumor latency inducedIAGP7,12-dimethyltetraphene (DMBA)compared to SS/JrHsdMcwiRGD 

Objects Annotated

QTLs
Mcs25  (Mammary carcinoma susceptibility QTL 25)
Mcs26  (Mammary carcinoma susceptibility QTL 26)
Mcs27  (Mammary carcinoma susceptibility QTL 27)

Objects referenced in this article
Strain SS-Chr 12BN/Mcwi null Rattus norvegicus
Strain SS.BN-(D13Rat111-D13Got22)/Mcwi null Rattus norvegicus
Strain SS.BN-(D13Rat151-D13Rat197)/Mcwi null Rattus norvegicus
Strain SS.BN-(D13Rat7-D13Rat60)/Mcwi null Rattus norvegicus

Additional Information