The prognostic significance of low-frequency somatic mutations in metastatic cutaneous melanoma

Background: Little is known about the prognostic significance of somatically mutated genes in metastatic melanoma (MM). We have employed a combined clinical and bioinformatics approach on tumor samples from cutaneous melanoma (SKCM) as part of The Cancer Genome Atlas project (TCGA) to identify mutated genes with potential clinical relevance. Methods: After limiting our DNA sequencing analysis to MM samples (n = 356) and to the CANCER CENSUS gene list, we filtered out mutations with low functional significance (snpEFF). We performed Cox analysis on 53 genes that were mutated in ≥3% of samples, and had ≥50% difference in incidence of mutations in deceased subjects versus alive subjects. Results: Four genes were potentially prognostic [RAC1, FGFR1, CARD11, CIITA; false discovery rate (FDR) 75% of the samples that exhibited corresponding DNA mutations. The low frequency, UV signature type and RNA expression of the 22 genes in MM samples were confirmed in a separate multi-institution validation cohort (n = 413). An underpowered analysis within a subset of this validation cohort with available patient follow-up (n = 224) showed that somatic mutations in SPEN and RAC1 reached borderline prognostic significance [log-rank favorable (p = 0.09) and adverse (p = 0.07), respectively]. Somatic mutations in SPEN, and to a lesser extent RAC1, were not associated with definite gene copy number or RNA expression alterations. High (>2+) nuclear plus cytoplasmic expression intensity for SPEN was associated with longer melanoma-specific overall survival (OS) compared to lower (≤ 2+) nuclear intensity (p = 0.048). We conclude that expressed somatic mutations in infrequently mutated genes beyond the well-characterized ones (e.g., BRAF, RAS, CDKN2A, PTEN, TP53), such as RAC1 and SPEN, may have prognostic significance in MM

O perfil dos ingressantes de um programa de educação física para idosos e os motivos da adesão inicial The profile of the initiators in a physical education program for elderly and the reasons for the initial adherence

Numa sociedade em pleno envelhecimento, a Educação Física deverá desempenhar um importante papel. A cada ano, cresce a procura por programas supervisionados, como é o caso do Programa Autonomia para Atividade Física do Idoso - PAAF. Conhecer o idoso é fundamental para orientar as ações pedagógicas e atender suas expectativas. Assim, este trabalho destina-se a conhecer o perfil sócio-demográfico, a atividade física pregressa, verificar a saúde percebida e entender quais foram os motivos de adesão ao programa. Participaram desse estudo 54 pessoas (14 homens e 40 mulheres), com idade acima de 60 anos (66,45 ± 5,176 anos de idade), que ingressaram no PAAF-2002. Foram utilizados questionários, em que foram consideradas as seguintes variáveis: gênero, idade, nível de escolaridade, estado civil; saúde percebida do ingressante; a atividade profissional e a atividade física pregressa e o nível sócio-econômico. Para verificar os motivos da adesão inicial utilizamos tabela tipo Liekert e aplicamos o Índice de Consistência Interna de Liekert. Utilizamos o Coeficiente de Concordância de Kendall (W) e o Teste de Friedman (Xr²), com nível de significância (p = 0,05). A maioria dos alunos tinha entre 60 a 70 anos de idade, pertencia aos níveis sócio-econômico A e B e possuía alto nível de escolaridade. A maioria tinha pelo menos uma doença, porém, a saúde percebida era positiva. Os motivos de adesão relatados foram: aprender fazer exercícios físicos, melhorar condicionamento físico e prevenir problemas de saúde. Já, ocupar o tempo livre e fazer amigos foram motivos considerados menos importantes..<br>In an aging society, Physical Education has paramount importance. Each year the search for supervised programs expends, as in the Elderly Physical Activity Autonomy Program (PAAP) case. Understanding the elderly is important to orientate the pedagogic actions and to attend participants' needs. Therefore, the purpose of this study was to determine the social demographic characteristics, previous physical activity, perceived health of the elderly and to understand the reasons for their adherence in the PAAP. Fifty four individuals (14 male and 40 female, 66,45 ± 5,176 years old) that went into PAAP took part in this study. Questionnaires were used with the following variables: type, age, education level, marital status, perceived health, previous professional activity, previous physical activity and social-economic level. To check the reasons for the first adherence, we used the Liekert table and the Liekert Internal Consistence Index. To confirm the results, we applied the Kendall Concordance Coefficient (W) and the Friedman test (Xr²), adopting p = 0.05 as the significance level. The majority of the participants belonged to the A and B socio-economical classes and had a bachelor's degree. The majority had, at least, one disease, but the perceived health was positive. The adherence reasons reported were: learn how to perform physical exercises, to improve physical condition and to prevent health problems. Further, take up free time and to make friends were considered the less important reasons