The TP53 website: an integrative resource centre for the TP53 mutation database and TP53 mutant analysis

Leroy, Bernard; Fournier, Jean Louis; Ishioka, Chikashi; Monti, Paola; Inga, Alberto; Fronza, Gilberto; Soussi, Thierry

doi:10.1093/nar/gks1033

Cited by 146 publications

(151 citation statements)

References 35 publications

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“…First, TP53 mutations can function differently in different cell contexts. For instance, the R175H nondisruptive mutant upregulated the transcription of the human telomerase reverse transcriptase gene in osteosarcoma cells, whereas it had no effect on a lung adenocarcinoma cell line (13). Second, we analyzed stage IIIB-IV, nonresectable lung cancer, while the patients in the HNSCC studies were all surgically resected.…”

Section: Discussionmentioning

confidence: 99%

“…13) and obtained using the MUT-TP53 2.0 Excel spreadsheet tool (22), which was also used to perform comparison of our dataset with previous publications using the mean and 95% confidence interval (CI) of p53 activity as measured by transactivation with the WAF1 promoter. In the validation cohort, the mean of our study was À1.27 for EGFR-wt and À1.34 for EGFR-mut, compared with À1.26 and À1.29 in the two comprehensive NSCLC studies reported in the tool.…”

Section: Analysis Of Tp53 Mutationsmentioning

confidence: 99%

“…Mechanisms of mutated p53 GOF include interference with p53-related proteins (p63, p73, etc; ref. 12) and aberrant upregulation of genes that promote cancer progression or drug resistance (13).…”

Section: Introductionmentioning

confidence: 99%

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Nondisruptive p53 Mutations Are Associated with Shorter Survival in Patients with Advanced Non–Small Cell Lung Cancer

Molina-Vila

Bertrán-Alamillo

Gasco

et al. 2014

Clinical Cancer Research

131

149

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Purpose: TP53 mutations in early-stage non-small cell lung cancer (NSCLC) may be associated with worse survival but their prognostic role in advanced NSCLC is controversial. In addition, it remains unclear whether mutated patients represent a clinically homogeneous group.Experimental Design: We retrospectively examined TP53 mutations and outcome in a training cohort of 318 patients with stage IIIB-IV NSCLC: 125 epidermal growth factor receptor (EGFR) wild-type (wt) and 193 EGFR mutated (mut). An independent validation cohort of 64 EGFR-mut patients was subsequently analyzed. Mutations were classified as "disruptive" and "nondisruptive" according to their predicted degree of disturbance of the p53 protein structure and function.Results: In the training cohort, TP53 mutations were found in 43 of the 125 EGFR-wt patients (34.4%). Of these, 28 had nondisruptive TP53 mutations and a median overall survival (OS) of 8.5 months, compared with 15.6 months for the remaining 97 patients (P ¼ 0.003). In the EGFR-mut group, TP53 mutations were found in 50 of the 193 patients (25.9%). The OS for the 26 patients with TP53 nondisruptive mutations was 17.8 months versus 28.4 months for the remaining 167 patients (P ¼ 0.04). In the validation cohort, the 11 patients with nondisruptive TP53 mutations had a median OS of 18.1 months compared with 37.8 months for the 53 remaining patients (P ¼ 0.006). In multivariate analyses, nondisruptive TP53 mutations had an independent, significant association with a shorter OS.Conclusions: Nondisruptive mutations in the TP53 gene are an independent prognostic factor of shorter survival in advanced NSCLC.

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Section: Discussionmentioning

confidence: 99%

Section: Analysis Of Tp53 Mutationsmentioning

confidence: 99%

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Nondisruptive p53 Mutations Are Associated with Shorter Survival in Patients with Advanced Non–Small Cell Lung Cancer

Molina-Vila

Bertrán-Alamillo

Gasco

et al. 2014

Clinical Cancer Research

131

149

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“…En los pacientes con sospecha del síndrome solía estudiarse únicamente la región que codifica el dominio de unión al ADN (exones 5 a 8), por ser un "punto caliente" para mutaciones deletéreas (5,8); no obstante, actualmente se recomienda estudiar toda la región codificante, así como las deleciones y duplicaciones, puesto que estas se encuentran en 1 a 5 % de los casos de síndrome de Li-Fraumeni.…”

Section: Discussionunclassified

Síndrome de Li-Fraumeni

Ossa

Molina

Cock-Rada³

2016

biomedica

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Contribución de los autores:Carlos Andrés Ossa: médico tratante, coordinación del estudio clínico y paraclínico del paciente Gustavo Molina: médico tratante Alicia María Cock-Rada: valoración oncogenética e interpretación de los resultados moleculares Todos los autores participaron en la escritura del manuscrito y en la búsqueda de bibliografía. El síndrome de Li-Fraumeni se caracteriza por la aparición de tumores en múltiples órganos, generalmente a temprana edad. Esta condición hereditaria es causada por mutaciones germinales en el gen TP53, que codifica el gen supresor tumoral p53. Se presenta el caso de una paciente de 31 años con diagnóstico clínico y molecular de síndrome de Li-Fraumeni, que presentó dos tumores sincrónicos a los 31 años: un leiomiosarcoma de antebrazo y un tumor filoides de mama. Tenía el antecedente de un hijo con diagnóstico de carcinoma cortical suprarrenal a los tres años, que falleció a los cinco años debido a la enfermedad. Además, su abuela y su bisabuela maternas habían fallecido de cáncer gástrico a los 56 y 60 años, respectivamente, y la madre y una hermana de su abuelo materno presentaron cáncer de mama pasados los 60 y los 40 años de edad, respectivamente. Después de una asesoría genética, se ordenó hacer la secuenciación completa y el análisis de duplicaciones y deleciones en el gen TP53. El estudio molecular en una muestra de ADN proveniente de linfocitos de sangre periférica reveló la mutación germinal c.527G>T (p.Cys176Phe) en el exón 5 del gen, mutación deletérea descrita anteriormente en tejidos tumorales. Hasta donde se sabe, este es el primer caso que se publica en Colombia de síndrome de Li-Fraumeni con diagnóstico molecular confirmado. El diagnóstico y el manejo del síndrome de Li-Fraumeni deben estar a cargo de un equipo multidisciplinario, y debe contarse con asesoría genética para el paciente y sus familiares. Síndrome de Li-FraumeniPalabras clave: síndrome de Li-Fraumeni, gen TP53, asesoramiento genético, síndromes neoplásicos hereditarios, tumor filoides, Colombia. doi: http://dx.doi.org/10.7705/biomedica.v36i3.2793 Li-Fraumeni syndromeThe Li-Fraumeni syndrome is characterized clinically by the appearance of tumors in multiple organs generally at an early age. This hereditary condition is caused by germinal mutations in the TP53 gene, which codifies for the tumoural suppressor gene p53. We present the case of a patient aged 31 with clinical and molecular diagnosis of Li-Fraumeni syndrome who presented two synchronous tumors: a leiomyosarcoma on the forearm and a phyllodes breast tumour. She had a family history of cancer, including a son diagnosed with a cortical adrenal carcinoma when he was three years old, who died at five from the disease. Furthermore, her maternal grandmother and great-grandmother died of stomach cancer at 56 and 60 years old, respectively, while her other greatgrandmother and a great aunt presented with breast cancer at the ages of 60 and 40, respectively. After genetic counseling, complete sequencing and analysis of duplications and delet...

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“…26,27 In hematological malignancies, TP53 mutations are relatively uncommon (around 10%), but wild-type p53 is often inactivated through the overexpression of MDM2. 28 Therefore, restoration of the functions of p53, and specifically its ability to induce apoptosis by disrupting MDM2-p53 binding, may be a promising therapeutic strategy.…”

Section: Introductionmentioning

confidence: 99%

Activation of wild-type p53 by MDM2 inhibitors: a new strategy for lymphoma treatment

Pujals¹,

Favre²,

Gaulard³

et al. 2015

BLCTT

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Abstract:The tumor suppressor TP53 is frequently mutated or inactivated in human cancers. Mutations of TP53 are less common in lymphomas than in other tumors, but the protein is often inhibited by the overexpression of its main regulator -MDM2. In the past 10 years, major efforts have been made to develop drugs that can reactivate p53 and restore its functions. This review focuses on recent advances in the development of small inhibitors of MDM2, which are potentially relevant for the treatment of B-and T-cell lymphomas. We will describe the current state of development of these drugs and discuss their mechanism of action in these hematological malignancies.

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The TP53 website: an integrative resource centre for the TP53 mutation database and TP53 mutant analysis

Cited by 146 publications

References 35 publications

Nondisruptive p53 Mutations Are Associated with Shorter Survival in Patients with Advanced Non–Small Cell Lung Cancer

Nondisruptive p53 Mutations Are Associated with Shorter Survival in Patients with Advanced Non–Small Cell Lung Cancer

Síndrome de Li-Fraumeni

Activation of wild-type p53 by MDM2 inhibitors: a new strategy for lymphoma treatment

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