RGD Reference Report - Disruptive TP53 mutation is associated with aggressive disease characteristics in an orthotopic murine model of oral tongue cancer. - Rat Genome Database

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Disruptive TP53 mutation is associated with aggressive disease characteristics in an orthotopic murine model of oral tongue cancer.

Authors: Sano, D  Xie, TX  Ow, TJ  Zhao, M  Pickering, CR  Zhou, G  Sandulache, VC  Wheeler, DA  Gibbs, RA  Caulin, C  Myers, JN 
Citation: Sano D, etal., Clin Cancer Res. 2011 Nov 1;17(21):6658-70. doi: 10.1158/1078-0432.CCR-11-0046. Epub 2011 Sep 8.
RGD ID: 8547850
Pubmed: PMID:21903770   (View Abstract at PubMed)
PMCID: PMC3207013   (View Article at PubMed Central)
DOI: DOI:10.1158/1078-0432.CCR-11-0046   (Journal Full-text)

PURPOSE: To characterize tumor growth and metastatic potential in head and neck squamous cell carcinoma (HNSCC) cell lines in an orthotopic murine model of oral tongue cancer and to correlate TP53 mutation status with these findings. EXPERIMENTAL DESIGN: Cells from each of 48 HNSCC cell lines were orthotopically injected into the oral tongues of nude mice. Tumor volume, cervical lymph node metastasis, and mouse survival were recorded. Direct sequencing of the TP53 gene and Western blot analysis for the p53 protein after induction with 5-fluorouracil was conducted. Cell lines were categorized as either mutant TP53 or wild-type TP53, and lines with TP53 mutation were further categorized on the basis of type of mutation (disruptive or nondisruptive) and level of p53 protein expression. The behavior of tumors in these different groups was compared. RESULTS: These 48 HNSCC cell lines showed a wide range of behavior from highly aggressive and metastatic to no tumor formation. Mice injected with cells harboring disruptive TP53 mutations had faster tumor growth, greater incidence of cervical lymph node metastasis, and shorter survival than mice injected with cells lacking these mutations. CONCLUSIONS: HNSCC cell lines display a wide spectrum of behavior in an orthotopic model of oral cancer. Cell lines with disruptive TP53 mutations are more aggressive in this system, corroborating clinical reports that have linked these mutations to poor patient outcome.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Tongue Neoplasms  IDA 8547850 RGD 
Tongue Neoplasms  ISOTP53 (Homo sapiens)8547850; 8547850 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tp53  (tumor protein p53)

Genes (Mus musculus)
Trp53  (transformation related protein 53)

Genes (Homo sapiens)
TP53  (tumor protein p53)


Additional Information