A TP53 founder mutation, p.R337H, is associated with phyllodes breast tumors in Brazil

Giacomazzi, Juliana; Koehler‐Santos, Patrícia; Palmero, Edenir Inêz; Graudenz, Márcia Silveira; Rivero, Luis Fernando; Lima, Eduardo Nóbrega Pereira; Pütten, Antonio Carlos Kruel; Hainaut, Pierre; Camey, Suzi Alves; Michelli, Rodrigo D.; Scapulatempo‐Neto, Cristovam; Fitarelli-Kiehl, Mariana; Geyer, G; Meurer, Luíse; Geiger, Ana; Azevedo, Monica Blaya; Silva, Vinícius Duval da; Ashton‐Prolla, Patrícia

doi:10.1007/s00428-013-1439-8

Cited by 25 publications

(18 citation statements)

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“…Preliminary results from Southern and Southeastern Brazil indicate that the mutation is present in the germline of a significant proportion of women with premenopausal breast cancer (Giacomazzi et al , 2011). In addition to the core tumors associated with Li-Fraumeni syndrome, p.R337H carriers also appear to be more prone to tumors not frequently reported in classic LFS patients, such as thyroid and gastric cancers and phyllodes tumors of the breast (Achatz et al , 2007; Giacomazzi et al , 2013). …”

Section: Resultsmentioning

confidence: 93%

Prevalence and impact of founder mutations in hereditary breast cancer in Latin America

Ashton‐Prolla

Vargas

2014

Genet. Mol. Biol.

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Approximately 10% of all cancers are considered hereditary and are primarily caused by germline, high penetrance mutations in cancer predisposition genes. Although most cancer predisposition genes are considered molecularly heterogeneous, displaying hundreds of different disease-causing sequence alterations, founder mutations have been identified in certain populations. In some Latin American countries, founder mutations associated with increased risk of breast and other cancers have been described. This is particularly interesting considering that in most of these countries, populations are highly admixed with genetic contributions from native populations and from the in-flux of several distinct populations of immigrants. In this article, we present a review of the scientific literature on the subject and describe current data available on founder mutations described in the most common breast cancer predisposition genes: BRCA1, BRCA2 and TP53.

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Section: Resultsmentioning

confidence: 93%

Prevalence and impact of founder mutations in hereditary breast cancer in Latin America

Ashton‐Prolla

Vargas

2014

Genet. Mol. Biol.

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“…The TP53 p.R337H founder allele has been identified in~0.3% of the general population of southern Brazil in two independent prevalence studies. In addition, it has been observed in the germline of more than 90% of the children diagnosed with choroid plexus and adrenocortical carcinomas and among women with phyllodes breast tumors, especially in those with malignant tumors (1)(2)(3)(4)(5)(6)(7)(8)15).…”

Section: Discussionmentioning

confidence: 99%

The Brazilian Founder MutationTP53p.R337H is Uncommon in Portuguese Women Diagnosed with Breast Cancer

et al. 2014

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Since the first studies reporting the TP53 p.R337H mutation as founder mutation in Southern and Southeastern Brazil, there has been controversy on its origin. Preliminary analysis of a small subset of Brazilian mutation carriers revealed that the haplotype incided on a Caucasian background. The vast majority of carriers identified today reside in Brazil or, if identified in other countries, are Brazilian immigrants. To our knowledge, the only two exceptions of carriers without a recognizable link with Brazil are two European families, from Portugal and Germany. Haplotype analysis in the Portuguese family revealed the same haplotype identified in Brazilian individuals, but in the German family, a distinct haplotype was found. Knowing that a significant proportion of women with breast cancer (BC) in Southern Brazil are p.R337H carriers, we analyzed p.R337H in a Portuguese cohort of women diagnosed with this disease. Median age at diagnosis among the first 573 patients tested was 60 years and 100 (17.4%) patients had been diagnosed at or under the age of 45 years. Mutation screening failed to identify the mutation in the 573 patients tested. These results are in contrast with the mutation frequency observed in a study including 815 BC-affected women from Brazil, in which carrier frequencies of 12.1 and 5.1% in pre- and postmenopausal women were observed, respectively. These findings suggest that the Brazilian founder mutation p.R337H, the most frequent germline TP53 mutation reported to date, is not a common germline alteration in Portuguese women diagnosed with BC.

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“…40 Positive cases were found in benign (n = 5) and malignant phyllodes breast tumors (n = 3); this suggests that this variant plays a role in phyllodes breast tumorigenesis. 40 Substantial clinical tumor heterogeneity and a wide range of tumor types have been observed at an increased frequency in TP53 p.R337H carriers. In an analysis of 45 unselected Brazilian patients (29 male) with nonsmall cell lung cancer treated at Hospital Júlia Kubitschek (Minas Gerais State), 4 (8.9%) were p.R337H carriers.…”

Section: The Intricate Cancer Phenotype Among Carriers Of the Foundermentioning

confidence: 96%

What 20 years of research has taught us about the TP53 p.R337H mutation

Pinto

Zambetti

2020

Cancer

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The p53 tumor suppressor transcriptionally regulates a myriad of genes involved in cell cycle control, DNA repair, cell survival, and cell metabolism and represents one of the most well-studied inhibitors of tumorigenesis. Since the discovery of TP53 in 1979, somatic mutations have been shown to be extremely common; more than 50% of human cancers carry loss-of-function mutations in TP53. Inherited or germline TP53 mutations are rare and are involved in complex hereditary cancer predisposition disorders, and affected family members can develop diverse tumor types and multiple primary cancers at young ages. In Brazil, a fascinating history of p53 and cancer predisposition began in the year 2000 with identification of the TP53 p.R337H mutation in close association with the development of adrenocortical tumors. In these past 20 years, much has been learned about the genetics and biochemistry of this mutation, which is widespread in Brazil because of a founder effect. This review highlights the contributions of TP53 p.R337H research over the last 20 years, the findings of which have sparked passionate debate among researchers worldwide, to understanding cancer predisposition in Brazilian individuals and families. Cancer 2020;126:4678-4686.

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A TP53 founder mutation, p.R337H, is associated with phyllodes breast tumors in Brazil

Cited by 25 publications

References 25 publications

Prevalence and impact of founder mutations in hereditary breast cancer in Latin America

Prevalence and impact of founder mutations in hereditary breast cancer in Latin America

The Brazilian Founder MutationTP53p.R337H is Uncommon in Portuguese Women Diagnosed with Breast Cancer

What 20 years of research has taught us about the TP53 p.R337H mutation

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