The Molecular Landscape of Medulloblastoma in Teenagers and Young Adults.
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ABSTRACT:
SUBMITTER: Mohammed OJ
PROVIDER: S-EPMC8750554 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Genome wide DNA methylation profiling of IDH-wildtype, H3-wildtype AYA glioblastomas
2022-02-12 | GSE196490 | GEO
Project description:Between 1979 and 2001, an analysis of cancer survival in young people in England, aged 13 to 24 years, showed overall improvements. However, for some diagnostic groups, little or no increases were observed. The aim of this study was to analyse the regional distribution of cancer survival in teenagers and young adults in England in order to identify patterns and potential for improvements at a regional scale.We examined geographical and temporal patterns in relative survival in cancer patients aged 13-24 years in England during the time period 1979-2001. Cancer cases were grouped according to an internationally recognised morphology-based diagnostic scheme.For most diagnostic groups, there was little variation in survival between regions, except for testicular germ cell tumours (P=0.006) and colorectal carcinoma (P=0.002). For certain diagnostic groups, the temporal pattern in survival differed between regions. However, in regions that showed poor survival during the early part of the study period, greatest improvements were observed in groups such as acute lymphoid leukaemia, acute myeloid leukaemia, testicular tumours and melanoma.In conclusion, there was a reduction in the differences in survival between regions during the study period.
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Project description:BACKGROUND:Medulloblastoma is the most common malignant brain tumor in children, currently treated uniformly based on histopathology and clinico-radiological risk stratification leading to unpredictable relapses and therapeutic failures. Identification of molecular subgroups have thrown light on the reasons for these and now reveals clues to profile molecularly based personalized therapy against these tumors. METHODS:Research and online contents were evaluated for pediatric medulloblastoma which included latest information on the molecular subgroups and their clinical relevance and update on efforts to translate them into clinics. RESULTS:Scientific endeavors over the last decade have clearly identified four molecular variants (WNT, SHH, Group 3, and Group 4) and their demographic, genomic, and epigenetic profile. Latest revelations include significant heterogeneity within these subgroups and 12 different subtypes of MB are now identified with disparate outcomes and biology. These findings have important implications for stratification and profiling future clinical trials against these formidable tumors. CONCLUSION:With the continued outpouring of genomic/epigenomic data of these molecular subgroups and evolution of further subtypes in each subgroup, the challenge lies in comprehensive evaluation of these informations. Current and future endeavors are now needed to profile personalized therapy for each child based on the molecular risk stratification of medulloblastoma, with a hope to improve survival outcome and reduce relapses.
| S-EPMC6120114 | biostudies-literature
Project description:For people with muscular dystrophy (MD) health care access is crucial and utilization is expected to be high. A multidisciplinary approach is needed for optimal management of symptoms of this rare condition. Regular primary care, specialty care, therapy, and medicine use can improve quality of care and reduce need for emergency treatment and hospitalization. We analyzed health insurance and administrative data to test for racial disparities in regular care use among teenagers and young adults with MD.We used South Carolina Medicaid and other administrative data for individuals aged 15-24 years to determine annual health care utilization patterns for individuals with MD by race. We studied adolescents and young adults with MD because this age group represents a time when the condition is typically intensifying and the transition from pediatric to adult care is expected. We used Generalized Estimating Equation models to analyze longitudinal utilization data conditional on other factors that may lead to utilization differences.Race is correlated with health care utilization among adolescents and young adults with MD. Blacks have lower overall utilization, and less primary care, therapy, and specialist care use but higher incidence of hospitalization and emergency treatment use compared with whites and also to other races. The most striking disparity was the use of outpatient services. Blacks utilized these services 50% less compared with whites and 70% less compared with others. Even in regression analysis, where we take into account individual unobserved factors and allow clustering at the individual level, these differences remained and were in most cases statistically significant.Our results indicate that there are differences in health care utilization by race even when individuals have access to the same health care benefits. This means simply offering coverage to individuals with MD may not be sufficient in eliminating health disparities. Future studies will be needed to examine other possible sources of these racial disparities, such as resource awareness, health knowledge, or access barriers such as transportation.
| S-EPMC4630026 | biostudies-literature
Project description:BackgroundTumours of the central nervous system are the second most common group of childhood cancers in 0-14 year olds (24% of total cancers) and represent a major diagnostic group in 15-24 year olds. The pilot case-control study aimed to establish methodologies for a future comprehensive aetiological investigation among children and young adults.MethodsEligible cases were newly diagnosed with an intracranial tumour of neuroepithelial tissue aged 0-24 years. The pilot recruited patients through Leeds and Manchester Principal Treatment Centres. Controls were drawn from general practice lists. Controls were frequency matched by age and gender.ResultsWe interviewed 49 cases and 78 controls comprising 85% of the target sample size. Response rates were 52% for cases and 32% for controls. Completion of the questionnaire was successful, with a very small proportion of missing data being reported (5-10%). The age distribution of cases and controls was similar with around three-quarters of interviewed subjects aged 0-14. Half of cases and almost two-thirds of controls reported using a mobile phone with the majority starting between 10-14 years of age. Prevalence of breastfeeding was lower in cases than controls (Odds Ratio 0.4; 95% CI 0.2-1.2), whilst cases were more likely to be delivered by caesarean section (OR 1.6; 95% CI 0.6-4.4). Cases were significantly more likely to have a birthweight > 3.5 kg compared to controls. Cases were also more likely to come from a family with 3 or more siblings than controls (OR 3.0; 95% CI 0.7-13.6). The majority of participants (>80%) were in favour of taking either blood or saliva to aid molecular epidemiological research.ConclusionsSuccessful methods were established for identifying and recruiting a high proportion of case subjects, exploiting strong links with the clinical teams at the treatment centres. Control procedures proved more difficult to implement. However, working closely with national clinical and professional research networks will enable improved control identification and recruitment, with good prospects for collecting biological samples in the future.
| S-EPMC3922821 | biostudies-literature
Project description:Most studies, aimed at determining the incidence and transmission of SARS-CoV-2 in children and teenagers, have been developed in school settings. Our study conducted surveillance and inferred attack rates focusing on the practice of sports. Prospective and observational study of those attending the sports facilities of Fútbol Club Barcelona (FCB), in Barcelona, Spain, throughout the 2020-2021 season. Participants were young players (from five different sports) and adult workers, who belonged to stable teams (shared routines and were involved in same quarantine rules). Biweekly health questionnaires and SARS-CoV-2 screening were conducted. From the 234 participants included, 70 (30%) both lived and trained in the FCB facilities (Recruitment Pathway 1;RP1) and 164 (70%) lived at their own household and just came to the facilities to train (RP2). During the study, 38 positive cases were identified; none had severe symptoms or needed hospitalization. The overall weekly incidence in the cohorts did not differ compared to the one expected in the community, except for 2 weeks when an outbreak occurred. The attack rate (AR) was three times higher for the participants from RP1, in comparison to those from RP2 (p < 0.01). A Basketball team showed a significant higher AR. Conclusion: Physical activities in stable teams are not related to an increased risk of transmission of SARS-CoV-2, since there were the same observed cases than expected in the community. The risk is higher in indoor sports (Basketball vs. Football), and in closed cohort living settings (RP1 vs. RP2). The fulfilment of preventive measures is essential. What is Known: • Despite the low numerical impact caused in paediatric hospitalizations during COVID-19 pandemic, the social impact has been maximum. • The transmission potential in children and teenagers is limited, and it had been widely demonstrated in school settings. What is New: • Group physical activities in children and teenagers are not also related to an increased risk of transmission of SARS-CoV-2, when preventive measures, such as washing hands, and screening protocols are applied. • Routine and semi-professional sports activities seem safe environments to promote during this pandemic.
| S-EPMC10010953 | biostudies-literature
Project description:Sonic hedgehog medulloblastoma encompasses a clinically and molecularly diverse group of cancers of the developing central nervous system. Here, we use unbiased sequencing of the transcriptome across a large cohort of 250 tumors to reveal differences among molecular subtypes of the disease, and demonstrate the previously unappreciated importance of non-coding RNA transcripts. We identify alterations within the cAMP dependent pathway (GNAS, PRKAR1A) which converge on GLI2 activity and show that 18% of tumors have a genetic event that directly targets the abundance and/or stability of MYCN. Furthermore, we discover an extensive network of fusions in focally amplified regions encompassing GLI2, and several loss-of-function fusions in tumor suppressor genes PTCH1, SUFU and NCOR1. Molecular convergence on a subset of genes by nucleotide variants, copy number aberrations, and gene fusions highlight the key roles of specific pathways in the pathogenesis of Sonic hedgehog medulloblastoma and open up opportunities for therapeutic intervention.
| S-EPMC7979819 | biostudies-literature
Project description:BackgroundTeenagers and young adults (TYA, 15-24 years) diagnosed with cancer report repeated visits to primary care before referral. We investigated associations of symptoms and consultation frequency in primary care with TYA cancers.MethodsPopulation-based, case-control study was carried out using data from the Clinical Practice Research Datalink (CPRD). A total of 1064 TYA diagnosed with cancer were matched to 13,206 controls. Symptoms independently associated with specific cancers were identified. Likelihood ratios (LRs) and positive predictive values (PPVs) were calculated.ResultsIn the 3 months before diagnosis, 397 (42.9%) cases consulted > or =4 times vs 593(11.5%) controls (odds ratio (OR): 12.1; 95% CI: 9.7, 15.1), yielding a PPV for any cancer of 0.018%. The LR of lymphoma with a head/neck mass was 434 (95% CI: 60, 3158), with a PPV of 0.5%. Corresponding figures in other cancers included - LR of leukaemia with lymphadenopathy (any site): 29 (95% CI: 8, 112), PPV 0.015%; LR of CNS tumour with seizure: 56 (95% CI: 19, 163), PPV 0.024%; and LR of sarcoma with lump/mass/swelling: 79 (95% CI: 24, 264), PPV 0.042%.ConclusionTeenagers and young adults with cancer consulted more frequently than controls in the 3 months before diagnosis. Primary care features of cancer match secondary care reports, but were of very low risk; nonetheless, some features increased the likelihood of cancer substantially and should be taken seriously when assessing TYA.
| S-EPMC3681013 | biostudies-literature
Project description:AimsSomatic complaints are a frequent cause for consultation in primary care. In a transcultural context, somatic complaints are typically associated with psychological distress. A recent review about somatic symptom disorders in adolescence showed some nosographic heterogeneity and outlined various etiological hypotheses (traumatic, environmental, or neurologic), separate from the cross-cultural considerations. Migrants' children encounter specific problems involving cultural mixing-issues of filiation (familial transmission) and affiliation (belonging to a group). This paper aims to provide a systematic review of somatization in transcultural contexts among teenagers and young adults, aged 13 to 24, over the past decade.MethodsThis review adheres to the quality criteria set forth by the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Two authors queried three English databases (Medline, PsycInfo, WebOfScience) about somatization in transcultural contexts (migrant or non-Western population) among teenagers (13-18), young adults (19-24), or both. The methodological process comprised articles selection, data extraction, and then the analysis of emerging themes. Setting selection criteria to limit the transcultural field was difficult.ResultsThe study analyzed 68 articles. We present a descriptive analysis of the results, centered on three main themes. First, the literature highlights a nosographic muddle reflected in the combination of anxious and depressive symptoms together with the highly variable symptomatology. Second, discrimination issues were prevalent among the migrant population. Lastly, the literature review points out possibilities for improving a care pathway and reducing the diagnostic delay induced by migrants' hesitancy about Western care and the recurrent use of inappropriate diagnostic criteria.ConclusionThis review discusses the links between the nosographic muddle described here and the diagnostic delays these patients experience and raises concerns about rigid diagnostic compartmentalization. The work of the psychiatrist Frantz Fanon is here useful to understand externalized symptoms resulting from physical and psychological confinement. Discrimination issues raise questions about the cultural counter-transference health professionals experience in dealing with young migrants. Defining healthcare professionals' representations about somatic complaints in a transcultural context might be a fruitful path to explore in future research.Protocol prospero registration numberCRD42021294132. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021294132.
| S-EPMC9358691 | biostudies-literature
Project description:Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets. Driver mutations were confidently assigned to most patients belonging to Group 3 and Group 4 medulloblastoma subgroups, greatly enhancing previous knowledge. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 and 'enhancer hijacking' events that activate PRDM6. Thus, the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma.
| S-EPMC5905700 | biostudies-literature