RGD Reference Report - Phenotypic reversion of rat neoplastic liver nodules is under genetic control. - Rat Genome Database

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Phenotypic reversion of rat neoplastic liver nodules is under genetic control.

Authors: De Miglio, MR  Simile, MM  Muroni, MR  Calvisi, DF  Virdis, P  Asara, G  Frau, M  Bosinco, GM  Seddaiu, MA  Daino, L  Feo, F  Pascale, RM 
Citation: De Miglio MR, etal., Int J Cancer 2003 May 20;105(1):70-5.
RGD ID: 629574
Pubmed: PMID:12672032   (View Abstract at PubMed)
DOI: DOI:10.1002/ijc.11044   (Journal Full-text)

Low DNA synthesis and high redifferentiation (remodeling) characterize neoplastic nodules induced by chemical carcinogens in hybrid BFF1 rats, generated by crossing the susceptible F344 and resistant BN strains. We performed whole-genome scanning of BFF2 rats to identify loci controlling remodeling of nodules induced, 32 weeks after initiation with diethylnitrosamine, by the RH protocol. Remodeling nodules were identified as areas lacking uniformity of GST-P immunostaining and with irregular margins. Two loci in suggestive linkage with the percentage of remodeling nodules were identified on chromosomes 7 and 1 (LOD scores 3.85 and 2.9 at D7Rat25 and D1Mgh14). Significant dosage-negative effect of the B allele on remodeling and additive interaction between these loci were found. Significant epistatic interactions, showing a recessive, remodeling-enhancing effect of B alleles, occurred between D1Mit3 and D11Rat11 (corrected p = 0.0013) and between D6Rat14 and D8Rat46 (corrected p = 0.028). These data show that remodeling of neoplastic nodules during rat hepatocarcinogenesis is under genetic control. Loci affecting remodeling map to chromosomal regions syntenic to chromosomal segments of human HCC showing structural abnormalities.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Liver Neoplasms  IDA 629574; 629574 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
decreased liver tumor incidence  IDA 629574; 629574 RGD 

Objects Annotated

QTLs
Lnnr1  (Liver neoplastic nodule remodeling QTL 1)
Lnnr2  (Liver neoplastic nodule remodeling QTL 2)

Strains
BN  (BN)
F344/NRrrc  (NA)

Objects referenced in this article
Strain BN/Crli null Rattus norvegicus
Strain F344/Crli null Rattus norvegicus

Additional Information