👤 Kouki Tomida

Glioblastoma, isocitrate dehydrogenase wildtype (GBM, IDH-wt), is a highly aggressive brain tumor with a poor prognosis. Alterations in the fibroblast growth factor receptor (FGFR) gene family-such as FGFR::TACC fusions and FGFR1 mutations-have emerged as potential therapeutic targets; however, their clinical and genetic features in GBM, IDH-wt remain unclear. We analyzed 1076 GBM, IDH-wt cases using comprehensive genomic profiling data from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database in Japan. FGFR alterations were detected in 8.0% of patients, including FGFR::TACC fusions (3.3%) and FGFR1 mutations (2.9%). The FGFR::TACC fusion-positive group was older at diagnosis and showed higher frequencies of TERT promoter mutation and MDM2 amplification, and lower frequencies of EGFR amplification and TP53 mutation, compared with the fusion-negative group. The FGFR1 mutation-positive group was enriched for ATRX, NF1, and PIK3CA mutations and had significantly fewer TERT promoter and PTEN mutations, compared with the mutation-negative group. No significant differences in overall survival were observed, although both groups tended to have longer median overall survival compared with their respective negative groups. This study represents the largest genomic cohort to date of FGFR alterations in GBM, IDH-wt. FGFR::TACC fusion-positive and FGFR1 mutation-positive GBMs exhibited distinct genetic profiles, highlighting the clinical relevance of molecular subclassification and providing insight for future therapeutic strategies. Show less

The mutual effects of different activity intensities in daily life, such as sedentary behavior (SB) and physical activity (PA), on dementia onset are not yet fully understood. The purpose of this study was to examine the association between replacing SB with PA and the risk of dementia in older adults by using the isotemporal substitution (IS) model. Prospective cohort study. Community-dwelling older adults living without dementia in Takahama, were enrolled, interviewed, and physically examined. Follow-up data were collected from the Japanese Public Health Insurance and/or Long-Term Care Insurance system databases during follow-up. SB and PA data [light-intensity PA (LPA) and moderate-to-vigorous PA (MVPA)] were measured using a triaxial accelerometer for 14 days, and the average daily time for SB and PA was calculated in 10-minute increments. Participants were followed up monthly for new-onset dementia over 5 years. Cox proportional-hazards regression analysis was performed by using IS to estimate the effect of replacing one activity with another on the dementia onset. We included 1664 participants (mean ± standard deviation age, 73.1 ± 5.9 years) in this study. Over 5 years, 128 of 1664 participants developed dementia. Replacing 10 min/d of SB with LPA (hazard ratio, 0.86; 95% CI, 0.75-0.99) or MVPA (0.84; 0.74-0.96) was associated with a lower risk of dementia. Replacing 10 minutes of SB with LPA or MVPA was associated with a lower risk of dementia. Feasible behavioral changes in daily life may lead to a healthy life expectancy. Show less