The Brazilian TP53 mutation (R337H) and sarcomas Volc, Sahlua Miguel; Ramos, Cíntia Regina Niederauer; Galvão, Henrique de Campos Reis ...
PloS one,
01/2020, Volume:
15, Issue:
1
Journal Article
Peer reviewed
Open access
Sarcomas represent less than 1% of all solid neoplasms in adults and over 20% in children. Their etiology is unclear, but genetic susceptibility plays an important role in this scenario. Sarcoma is ...central in Li-Fraumeni Syndrome (LFS), a familial predisposition cancer syndrome. In Brazil, the high prevalence of p.Arg337His mutations in the TP53 gene brings about a unique condition: a cluster of LFS. In the present work, we studied 502 sarcoma patients not selected by age or family history in an attempt to assess the impact of the so-called "Brazilian germline TP53 mutation" (p.Arg337His) on this tumor type. We found that 8% of patients are carriers, with leiomyosarcoma being the main histologic type of sarcoma, corresponding to 52.5% of the patients with the mutated TP53 gene. These findings emphasize the importance of genetic counseling and can better guide the management of sarcoma patients.
Lynch syndrome (LS) is a hereditary cancer-predisposing syndrome associated most frequently with epithelial tumors, particularly colorectal (CRC) and endometrial carcinomas (EC). The aim of this ...study was to investigate the relationship between sarcomas and LS by performing clinical and molecular characterization of patients presenting co-occurrence of sarcomas and tumors from the LS spectrum. We identified 27 patients diagnosed with CRC, EC, and other LS-associated tumors who had sarcomas in the same individuals or families. Germline genetic testing, mismatch repair (MMR) protein immunohistochemistry, microsatellite instability (MSI), and other molecular analyses were performed. Five LS patients presenting personal or family history of sarcomas were identified (3 MSH2 carriers and 2 MLH1), with 2 having Muir–Torre phenotypes. For two MSH2 carriers we confirmed the etiology of the sarcomas (one liposarcoma and two osteosarcomas) as LS-related, since the tumors were MSH2/MSH6-deficient, MSI-high, or presented a truncated MSH2 transcript. Additionally, we reviewed 43 previous reports of sarcomas in patients with LS, which revealed a high frequency (58%) of MSH2 alterations. In summary, sarcomas represent a rare clinical manifestation in patients with LS, especially in MSH2 carriers, and the analysis of tumor biological characteristics can be useful for definition of tumor etiology and novel therapeutic options.
Li-Fraumeni and Li-Fraumeni-like syndrome (LFS/LFL) are clinically heterogeneous cancer predisposition syndromes characterized by diagnosis of early-onset and often multiple cancers with variable ...tumor patterns and incomplete penetrance. To date, the genetic modifiers described in LFS/LFL have been shown to map to either
TP53
or its main negative regulator,
MDM2
. Additionally, all studies were focused on families with different
TP53
germline mutations. Hence, in this study we explored the effect of the most studied polymorphisms of p53 pathway genes on clinical manifestations of individuals carrying the founder
TP53
mutation R337H (n = 136) and controls (n = 186). Cancer-affected carriers had been diagnosed either with adrenocortical carcinoma (ACC, n = 29) or breast cancer (BC, n = 43). Allelic discrimation using TaqMan assay was used for genotyping
MDM2
SNP 309 (rs2279744) as well as
MDM4
(rs1563828) and
USP7
(rs1529916) polymorphisms. We found significantly higher
MDM2
SNP 309 GG genotype and G allele frequencies in the LFS cohort than in controls. Furthermore, median age at first diagnosis was earlier in
MDM2
SNP309 GG carriers when compared to other genotypes for both cancers (ACC: age 1 vs. 2 years; BC: age 35 vs. 43 years, respectively), although not statistically different. The allelic and genotypic frequencies for all SNPs did not differ between cancer affected and unaffected carriers, neither between patients with ACC or BC. In conclusion, our results suggest that MDM2 SNP 309 may contribute to the LFL phenotype and also to an earlier age at diagnosis of ACC and BC cancer in carriers of the R337H founder mutation.
The Brazilian TP53 mutation Volc, Sahlua Miguel; Ramos, Cíntia Regina Niederauer; Galvão, Henrique de Campos Reis ...
PloS one,
01/2020, Volume:
15, Issue:
1
Journal Article
Peer reviewed
Sarcomas represent less than 1% of all solid neoplasms in adults and over 20% in children. Their etiology is unclear, but genetic susceptibility plays an important role in this scenario. Sarcoma is ...central in Li-Fraumeni Syndrome (LFS), a familial predisposition cancer syndrome. In Brazil, the high prevalence of p.Arg337His mutations in the TP53 gene brings about a unique condition: a cluster of LFS. In the present work, we studied 502 sarcoma patients not selected by age or family history in an attempt to assess the impact of the so-called "Brazilian germline TP53 mutation" (p.Arg337His) on this tumor type. We found that 8% of patients are carriers, with leiomyosarcoma being the main histologic type of sarcoma, corresponding to 52.5% of the patients with the mutated TP53 gene. These findings emphasize the importance of genetic counseling and can better guide the management of sarcoma patients.
O presente trabalho trata sobre a utilização do sistema de informação geográfica para analisar a ocorrência de câncer no estado de Santa Catarina entre dezembro de 2009 e dezembro de 2012. Apoiou-se ...em duas das principais abordagens metodológicas em Geografia da Saúde: "a abordagem ecológica das doenças" e a "abordagem espacial das doenças". Em ambiente SIG se fez a integração de dados socioambientais com dados de câncer para todos os municípios catarinenses, permitindo a criação de um importante instrumento para análises espaciais. Pode-se visualizar através de mapas temáticos diversas relações entre fatores geográficos e epidemiológicos do câncer. A utilização do SIG permitiu a criação de um importante instrumento de apoio para avaliação de riscos e tomadas de decisão em Saúde Pública.
O presente trabalho trata sobre a utilização do sistema de informação geográfica para analisar a ocorrência de câncer no estado de Santa Catarina entre dezembro de 2009 e dezembro de 2012. Apoiou-se ...em duas das principais abordagens metodológicas em Geografia da Saúde: "a abordagem ecológica das doenças" e a "abordagem espacial das doenças". Em ambiente SIG se fez a integração de dados socioambientais com dados de câncer para todos os municípios catarinenses, permitindo a criação de um importante instrumento para análises espaciais. Pode-se visualizar através de mapas temáticos diversas relações entre fatores geográficos e epidemiológicos do câncer. A utilização do SIG permitiu a criação de um importante instrumento de apoio para avaliação de riscos e tomadas de decisão em Saúde Pública.
Introdução: A população de adolescentes e adultos jovens com faixa etária entre 15 e 39 anos de idade diagnosticados com câncer é conhecida como AYA (adolescent and young adults). Esses ...pacientes recebem tratamento em centros pediátricos e de adultos, que não atendem às suas necessidades biológicas e sociais.
Objetivo: Identificar particularidades e demandas para o atendimento do paciente oncológico pertencente ao grupo AYA, a fim de configurar melhor atendimento.
Método: Trata-se de estudo quantitativo transversal. Utilizou-se um questionário traduzido e validado.
Resultados: Quarenta e cinco pacientes responderam ao questionário e os resultados foram reportados de forma descritiva. Foram consideradas como muito importantes questões sobre manutenção de dieta saudável durante o tratamento, exercícios físicos e condicionamento físico, além do aconselhamento psicológico; 38% apresentaram depressão ou transtorno de ansiedade associados.
Conclusão: Foi possível identificar as demandas da população AYA, essencial para a perspectiva futura de desenvolvimento de protocolos de acompanhamento com interdisciplinaridade.
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