An inherited
            <i>p53</i>
            mutation that contributes in a tissue-specific manner to pediatric adrenal cortical carcinoma

Ribeiro, Raul C.; Sandrini, Fabiano; Figueiredo, Bonald C.; Zambetti, Gerard P.; Michalkiewicz, Edson; Lafferty, Antony; DeLacerda, Luiz; Rabin, Mark; Cadwell, Craig; Sampaio, Gilberto Antunes; Cat, Izrail; Stratakis, Constantine A.; Sandrini, Romolo

doi:10.1073/pnas.161479898

Cited by 494 publications

(455 citation statements)

References 36 publications

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“…Additionally, the estimated penetrance of the mutant allele was approximately 10% (Figueiredo et al, 2006;Wasserman et al, 2012). Although the mutation was found in nearly 100% of cases of ACT (Ribeiro et al, 2001), its frequency in the general population outside South and Southeast Brazil was low (Pianovski et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

R337H mutation of the TP53 gene as a clinical marker in cancer patients: a systematic review of literature

2015

Genet. Mol. Res.

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ABSTRACT. The germline R337H mutation of the TP53 gene has been associated with the development of many tumor types. This systematic review of literature investigated the association between the R337H mutation and the patients' family history and its predictive and prognostic value in cancer. Data were collected from articles archived in the PubMed, LILACS, MEDLINE, IBECS, and SciELO databases. The systematic review of literature was performed on 12 selected articles, describing a total of 175,462 individuals tested for the R337H mutation, including 1548 individuals with cancer and 118 individuals with a family history of Li-Fraumeni and LiFraumeni-like syndrome. Eight studies showed an association between the mutation and a family history of cancer in 411 patients, including 390 cases of cancer among family members. Patients with the homozygous mutant genotype experienced cancer recurrence, progressive disease, secondary cancer, and a short survival rate. Heterozygous patients showed a better response to treatment and increased survival rates than did patients with 17035©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 17034-17043 (2015) R337H mutation of TP53 as a clinical marker in cancer the homozygous mutant genotype from newborns to adult patients. In conclusion, the R337H mutation has significant predictive and prognostic value and is associated with tumorigenesis of the adrenal cortex.

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Section: Discussionmentioning

confidence: 99%

R337H mutation of the TP53 gene as a clinical marker in cancer patients: a systematic review of literature

2015

Genet. Mol. Res.

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“…This process was found to be enhanced for the " hot-spot" R248Q contact and structural mutant, which is one of many changes in this domain known to destabilize the native structure (47). The other is for the R337H mutation in the tetramerization domain (48,49), which is associated with adrenocortical carcinoma (ACC) in children from southern Brazil (50). Both the WT and mutant peptides formed amyloid-like fibrils when incubated at pH 4.0 and elevated temperatures, with the mutant being susceptible at a lower temperature.…”

Section: Discussionmentioning

confidence: 99%

Unfolding, Aggregation, and Amyloid Formation by the Tetramerization Domain from Mutant p53 Associated with Lung Cancer

et al. 2006

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The p53 tumor suppressor is a tetrameric transcriptional enhancer, and its activity is compromised by mutations that cause amino acid substitutions in its tetramerization domain. Here we analyze the biochemical and biophysical properties of peptides corresponding to amino acids 319 to 358 of wildtype human p53, which includes the tetramerization domain, and that of a cancer-derived mutant with valine substituted for glycine 334. Unlike the wild-type peptide, the G334V peptide forms amyloid fibrils by a two step process under physiological conditions of temperature and pH. Nevertheless, the G334V peptide is capable of forming hetero-oligomers with a wild-type peptide. Computational modeling of the G334V peptide structure suggests that substitution of valine for glycine 334 causes a local distortion that contributes to a β-dominated structural transition leading to amyloid formation. Since the distortion is mostly on the surface, the mutant peptide is still able to form a pseudo-native tetramer complex at higher concentrations and/or lower temperatures. Our † KS was supported in

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“…12 From 1996 to 1999 a subset of 92 children with ACC treated at a single institution in southern Brazil underwent genotyping of p53 and were found to have an identical point mutation in exon 10 encoding an arginine-to-histidine amino acid substitution at codon 337 of p53. 24 Although half of first-degree and a third of second-degree relatives had a similar point mutation, there was no family history of cancers to suggest Li-Fraumeni syndrome. 11 Functional studies of the protein derived from the mutated p53 gene revealed that p53 in these patients had normal activity except at high pH, which can be found in the adrenal cortex in its physiologic state, a finding that partially explained the tissue-specific cancer predisposition.…”

Section: Adrenocortical Carcinoma and Retinoblastoma As Models Of Thementioning

confidence: 99%

Childhood cancer epidemiology in low‐income countries

Howard

Metzger

Wilimas

et al. 2007

Cancer

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238

183

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Global studies of childhood cancer provide clues to cancer etiology, facilitate prevention and early diagnosis, identify biologic differences, improve survival rates in low-income countries (LIC) by facilitating quality improvement initiatives, and improve outcomes in high-income countries (HIC) through studies of tumor biology and collaborative clinical trials. Incidence rates of cancer differ between various ethnic groups within a single country and between various countries with similar ethnic compositions. Such differences may be the result of genetic predisposition, early or delayed exposure to infectious diseases, and other environmental factors. The reported incidence of childhood leukemia is lower in LIC than in more prosperous countries. Registration of childhood leukemia requires recognition of symptoms, rapid access to primary and tertiary medical care (a pediatric cancer unit), a correct diagnosis, and a data management infrastructure. In LIC, where these services are lacking, some children with leukemia may die before diagnosis and registration. In this environment, epidemiologic studies would seem to be an unaffordable luxury, but in reality represent a key element for progress. Hospital-based registries are both feasible and essential in LIC, and can be developed using available training programs for data managers and the free online Pediatric Oncology Networked Data Base (www.POND4kids.org), which allows collection, analysis, and sharing of data.

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An inherited p53 mutation that contributes in a tissue-specific manner to pediatric adrenal cortical carcinoma

Cited by 494 publications

References 36 publications

R337H mutation of the TP53 gene as a clinical marker in cancer patients: a systematic review of literature

R337H mutation of the TP53 gene as a clinical marker in cancer patients: a systematic review of literature

Unfolding, Aggregation, and Amyloid Formation by the Tetramerization Domain from Mutant p53 Associated with Lung Cancer

Childhood cancer epidemiology in low‐income countries

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