Detection of R337H, a germline TP53 mutation predisposing to multiple cancers, in asymptomatic women participating in a breast cancer screening program in Southern Brazil

Palmero, Edenir Inêz; Schüler‐Faccini, Lavínia; Caleffi, Maira; Achatz, Maria Isabel; Olivier, Magalí; Martel‐Planche, Ghyslaine; Marcel, Virginie; Aguiar, Ernestina Silva de; Giacomazzi, Juliana; Ewald, Ingrid Petroni; Giugliani, Roberto; Hainaut, Pierre; Ashton‐Prolla, Patrícia

doi:10.1016/j.canlet.2007.10.044

Cited by 106 publications

(108 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This strongly indicates co-segregation between these markers and the R337H germline mutation. Additionally, the mutation may have originated from the founder effect in a common ancestor of most Brazilian patients with ACT (Pinto et al, 2004;Palmero et al, 2008). Analysis of inheritance patterns of families in Paraná State suggested that the R337H mutant allele emerged at least 110 years ago (Figueiredo et.…”

Section: Discussionmentioning

confidence: 99%

“…The association between the mutation, the emergence of different tumor types, and the high number of carriers make the R337H mutation an important factor in public health, particularly in predicting cancer (Achatz, 2008;Palmero et al, 2008;Achatz et al, 2009). The incidence of cancer at an early age resulting from the R337H mutation represents up to 5% of all cancers before the age of 70 and 5-10% of all cancers in children and young adults in southern Brazil.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

2015

Genet. Mol. Res.

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

2015

Genet. Mol. Res.

View full text Add to dashboard Cite

show abstract

“…We found three articles that studied variations in TP53, all in Brazilian populations [31,84,85]. These articles studied the c.1010G>A (p.R337H) mutation, which occurs at a high frequency in southern and southeastern Brazil [86][87][88][89][90]. Silva et al [31] reported a frequency of 2.5% for this variant and suggested that all BRCA-negative female BC patients with clinical criteria for hereditary breast-ovarian cancer should be tested for the c.1010G>A variant.…”

Section: Other Bc Susceptibility Mutations In Central and South Amerimentioning

confidence: 99%

Mutations in BRCA1, BRCA2 and other breast and ovarian cancer susceptibility genes in Central and South American populations

et al. 2017

View full text Add to dashboard Cite

Breast cancer (BC) is the most common malignancy among women worldwide. A major advance in the understanding of the genetic etiology of BC was the discovery of BRCA1 and BRCA2 (BRCA1/2) genes, which are considered high-penetrance BC genes. In non-carriers of BRCA1/2 mutations, disease susceptibility may be explained of a small number of mutations in BRCA1/2 and a much higher proportion of mutations in ethnicity-specific moderate-and/or low-penetrance genes. In Central and South American populations, studied have focused on analyzing the distribution and prevalence of BRCA1/2 mutations and other susceptibility genes that are scarce in Latin America as compared to North America, Europe, Australia, and Israel. Thus, the aim of this review is to present the current state of knowledge regarding pathogenic BRCA variants and other BC susceptibility genes. We conducted a comprehensive review of 47 studies from 12 countries in Central and South America published between 2002 and 2017 reporting the prevalence and/or spectrum of mutations and pathogenic variants in BRCA1/2 and other BC susceptibility genes. The studies on BRCA1/2 mutations screened a total of 5956 individuals, and studies on susceptibility genes analyzed a combined sample size of 11,578 individuals. To date, a total of 190 different BRCA1/2 pathogenic mutations in Central and South American populations have been reported in the literature. Pathogenic mutations or variants that increase BC risk have been reported in the following genes or genomic regions: ATM, BARD1, CHECK2, FGFR2, GSTM1, MAP3K1, MTHFR, PALB2, RAD51, TOX3, TP53, XRCC1, and 2q35.

show abstract

“…For example, mutations in the carboxyl-terminal oligomerization domain and, in particular, the R337H residue, have been noted to be prevalent in the Brazilian LFS patients, giving rise to a variety of tumor types (8), and especially adrenocortical carcinomas in children (9). This particular mutation causes defects in tetramer formation leading to loss of function (10), thereby highlighting other possible avenues by which mutations can inactivate p53 functionally.…”

mentioning

confidence: 99%

Amino-terminal p53 mutations lead to expression of apoptosis proficient p47 and prognosticate better survival, but predispose to tumorigenesis

Phang

Othman

Bougeard

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Whereas most mutations in p53 occur in the DNA-binding domain and lead to its functional inactivation, their relevance in the amino-terminal transactivation domain is unclear. We show here that amino-terminal p53 (ATp53) mutations often result in the abrogation of full-length p53 expression, but concomitantly lead to the expression of the aminoterminally truncated p47 isoform. Using genetically modified cancer cells that only express p47, we demonstrate it to be up-regulated in response to various stimuli, and to contribute to cell death, through its ability to selectively activate a group of apoptotic target genes. Target gene selectivity is influenced by K382 acetylation, which depends on the amino terminus, and is required for recruitment of selective cofactors. Consistently, cancers capable of expressing p47 had a better overall survival. Nonetheless, retention of the apoptotic function appears insufficient for tumor suppression, because these mutations are also found in the germ line and lead to Li-Fraumeni syndrome. These data from ATp53 mutations collectively demonstrate that p53's apoptosis proficiency is dispensable for tumor suppression, but could prognosticate better survival.amino terminus | ATp53 mutants | acetylation | p47 | full-length p53

show abstract

Detection of R337H, a germline TP53 mutation predisposing to multiple cancers, in asymptomatic women participating in a breast cancer screening program in Southern Brazil

Cited by 106 publications

References 11 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

Mutations in BRCA1, BRCA2 and other breast and ovarian cancer susceptibility genes in Central and South American populations

Amino-terminal p53 mutations lead to expression of apoptosis proficient p47 and prognosticate better survival, but predispose to tumorigenesis

Contact Info

Product

Resources

About