6533b7dcfe1ef96bd127338c
RESEARCH PRODUCT
Functional categories of TP53 mutation in colorectal cancer: results of an International Collaborative Study.
Iacopetta BAntonio RussoViviana BazanDardanoni GNicolo' GebbiaSoussi TKerr DElsaleh HSoong RKandioler DJanschek EKappel SLung MLeung CsKo JmYuen SHo JLeung SyCrapez EDuffour JYchou MLeahy DtO'donoghue DpValentina AgneseSandra CascioGaetana Di FedeChieco Bianchi LBertorelle RBelluco CGiaretti WCastagnola PRicevuto EFicorella CBosari SCarmela Rosaria ArizziM MiyakiOnda MKampman EDiergaarde BRoyds JLothe RaDiep CbMeling GiOstrowski JTrzeciak LGuzinska Ustymowicz KZalewski BCapella GmV MorenoPeinado MaLonnroth CLundholm KSun XfJansson ABouzourene HLl HsiehTang RSmith DrAllen Mersh TgKhan ZaShorthouse AjSilverman MlS KatoIshioka CTp Crc Collaborative Groupsubject
Oncologyp53MaleNutrition and Diseasebinding domainsLymphovascular invasionColorectal cancerDNA Mutational AnalysisAetiology screening and detection [ONCOL 5]Gene mutationmedicine.disease_causeTransactivationVoeding en ZiekteAntineoplastic Combined Chemotherapy ProtocolsDeterminants in Health and Disease [EBP 1]transcriptional activityMutationHematologyExonsMiddle AgedSurvival RateOncologyAdenocarcinomaFemaleColorectal Neoplasmsmedicine.medical_specialtyAdenocarcinomachemotherapy colorectal cancer mutation prognosis TP53 transactivational abilityMolecular epidemiology [NCEBP 1]Breast cancerTranslational research [ONCOL 3]Interventional oncology [UMCN 1.5]Internal medicinemedicineHumansNeoplasm InvasivenessSurvival rateneoplasmsbreast-cancerVLAGAgedNeoplasm StagingHereditary cancer and cancer-related syndromes [ONCOL 1]business.industryInternational Agenciesmedicine.diseaseImmunologyMutationTumor Suppressor Protein p53businessFollow-Up Studiesdescription
Item does not contain fulltext BACKGROUND: Loss of TP53 function through gene mutation is a critical event in the development and progression of many tumour types including colorectal cancer (CRC). In vitro studies have found considerable heterogeneity amongst different TP53 mutants in terms of their transactivating abilities. The aim of this work was to evaluate whether TP53 mutations classified as functionally inactive (< or=20% of wildtype transactivation ability) had different prognostic and predictive values in CRC compared with mutations that retained significant activity. MATERIALS AND METHODS: TP53 mutations within a large, international database of CRC (n = 3583) were classified according to functional status for transactivation. RESULTS: Inactive TP53 mutations were found in 29% of all CRCs and were more frequent in rectal (32%) than proximal colon (22%) tumours (P < 0.001). Higher frequencies of inactive TP53 mutations were also seen in advanced stage tumours (P = 0.0003) and in tumours with the poor prognostic features of vascular (P = 0.006) and lymphatic invasion (P = 0.002). Inactive TP53 mutations were associated with significantly worse outcome only in patients with Dukes' stage D tumours (RR = 1.71, 95%CI 1.25-2.33, P < 0.001). Patients with Dukes' C stage tumours appeared to gain a survival benefit from 5-fluorouracil-based chemotherapy regardless of TP53 functional status for transactivation ability. CONCLUSIONS: Mutations that inactivate the transactivational ability of TP53 are more frequent in advanced CRC and are associated with worse prognosis in this stage of disease.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2006-01-01 |