Transitions in mental health and addiction care for youth and their families: a scoping review of needs, barriers, and facilitators

Abstract Introduction Transitional-aged youth (TAY) with mental health and/or addictions (MHA) concerns and their families experience significant challenges finding, accessing, and transitioning through needed MHA care. To develop appropriate supports that assist TAY and their families in navigating MHA care, their experiences of transitions in the MHA care system must be better understood. This scoping review identifies and explores the needs, barriers, and facilitators for TAY and their families when transitioning through MHA care. Methods This scoping review commenced with a search of five relevant databases. Three research team members were involved in title, abstract, and full-text scanning and data extraction. Sources focusing on TAY anywhere between the ages of 12–29 years and meeting the study objectives were included. Extractions compiled background and narrative information about the nature and extent of the data. Analysis and synthesis of findings involved numerical description of the general information extracted (e.g., numbers of sources by country) and thematic analysis of narrative information extracted (e.g., family involvement in TAY help-seeking). Results A total of 5894 sources were identified. Following title and abstract scanning, 1037 sources remained for full-text review. A total of 66 sources were extracted. Findings include background information about extracted sources, in addition to five themes that emerged pertaining to barriers and facilitators to access and transitions through care and the needs and roles of TAY and families in supporting help-seeking and care transitions: holistic supports, proactive preparation, empowering TAY and families, collaborative relationships, and systemic considerations. These five themes demonstrate approaches to care that can ensure TAY and families’ needs are met, barriers are mitigated, and facilitators are enhanced. Conclusion This review provides essential contextual information regarding TAY with MHA concerns and their families’ needs when seeking care. Such findings lend to an enhanced understanding of how MHA programs can support this population’s needs, involve family members as appropriate, reduce the barriers experienced, and work to build upon existing facilitators

Integrated genomic characterization of endometrial carcinoma

We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumours and ~25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours.National Institutes of Health (U.S.) (Grant 5U24CA143799-04)National Institutes of Health (U.S.) (Grant 5U24CA143835-04)National Institutes of Health (U.S.) (Grant 5U24CA143840-04)National Institutes of Health (U.S.) (Grant 5U24CA143843-04)National Institutes of Health (U.S.) (Grant 5U24CA143845-04)National Institutes of Health (U.S.) (Grant 5U24CA143848-04)National Institutes of Health (U.S.) (Grant 5U24CA143858-04)National Institutes of Health (U.S.) (Grant 5U24CA143866-04)National Institutes of Health (U.S.) (Grant 5U24CA143867-04)National Institutes of Health (U.S.) (Grant 5U24CA143882-04)National Institutes of Health (U.S.) (Grant 5U24CA143883-04)National Institutes of Health (U.S.) (Grant 5U24CA144025-04)National Institutes of Health (U.S.) (Grant U54HG003067-11)National Institutes of Health (U.S.) (Grant U54HG003079-10)National Institutes of Health (U.S.) (Grant U54HG003273-10

Comprehensive molecular profiling of lung adenocarcinoma

Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen(mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis

Comprehensive molecular characterization of urothelial bladder carcinoma

Urothelial carcinoma of the bladder is a common malignancy that causes approximately 150,000 deaths per year worldwide. So far, no molecularly targeted agents have been approved for treatment of the disease. As part of The Cancer Genome Atlas project, we report here an integrated analysis of 131 urothelial carcinomasto provide a comprehensive landscape of molecular alterations. There were statistically significant recurrent mutations in 32 genes, including multiple genes involved in cell-cycle regulation, chromatin regulation, and kinase signalling pathways, as well as 9 genes not previously reported as significantly mutated in any cancer. RNA sequencing revealed four expression subtypes, two of which (papillary-like and basal/squamous-like) were also evident in microRNA sequencing and protein data. Whole-genome and RNA sequencing identified recurrent in-frame activating FGFR3-TACC3 fusions and expression or integration of several viruses (including HPV16) that are associated with gene inactivation. Our analyses identified potential therapeutic targets in 69% of the tumours, including 42% with targets in the phosphatidylinositol-3-OH kinase/AKT/mTOR pathway and 45% with targets (including ERBB2) in the RTK/MAPK pathway. Chromatin regulatory genes were more frequently mutated in urothelial carcinoma than in any other common cancer studied so far, indicating the future possibility of targeted therapy for chromatin abnormalitiesclose27

Comprehensive molecular profiling of lung adenocarcinoma

Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen(mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesisclose24

Comprehensive molecular profiling of lung adenocarcinoma: the cancer genome atlas research network

Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis

Comprehensive genomic characterization of squamous cell lung cancers

Lung squamous cell carcinoma is a common type of lung cancer, causing approximately 400,000 deaths per year worldwide. Genomic alterations in squamous cell lung cancers have not been comprehensively characterized, and no molecularly targeted agents have been specifically developed for its treatment. As part of The Cancer Genome Atlas, here we profile 178 lung squamous cell carcinomas to provide a comprehensive landscape of genomic and epigenomic alterations. We show that the tumour type is characterized by complex genomic alterations, with a mean of 360 exonic mutations, 165 genomic rearrangements, and 323 segments of copy number alteration per tumour. We find statistically recurrent mutations in 11 genes, including mutation of TP53 in nearly all specimens. Previously unreported loss-of-function mutations are seen in the HLA-A class I major histocompatibility gene. Significantly altered pathways included NFE2L2 and KEAP1 in 34%, squamous differentiation genes in 44%, phosphatidylinositol-3-OH kinase pathway genes in 47%, and CDKN2A and RB1 in 72% of tumours. We identified a potential therapeutic target in most tumours, offering new avenues of investigation for the treatment of squamous cell lung cancers.National Institutes of Health (U.S.) (Grant U24 CA126561)National Institutes of Health (U.S.) (Grant U24 CA126551)National Institutes of Health (U.S.) (Grant U24 CA126554)National Institutes of Health (U.S.) (Grant U24 CA126543)National Institutes of Health (U.S.) (Grant U24 CA126546)National Institutes of Health (U.S.) (Grant U24 CA126563)National Institutes of Health (U.S.) (Grant U24 CA126544)National Institutes of Health (U.S.) (Grant U24 CA143845)National Institutes of Health (U.S.) (Grant U24 CA143858)National Institutes of Health (U.S.) (Grant U24 CA144025)National Institutes of Health (U.S.) (Grant U24 CA143882)National Institutes of Health (U.S.) (Grant U24 CA143866)National Institutes of Health (U.S.) (Grant U24 CA143867)National Institutes of Health (U.S.) (Grant U24 CA143848)National Institutes of Health (U.S.) (Grant U24 CA143840)National Institutes of Health (U.S.) (Grant U24 CA143835)National Institutes of Health (U.S.) (Grant U24 CA143799)National Institutes of Health (U.S.) (Grant U24 CA143883)National Institutes of Health (U.S.) (Grant U24 CA143843)National Institutes of Health (U.S.) (Grant U54 HG003067)National Institutes of Health (U.S.) (Grant U54 HG003079)National Institutes of Health (U.S.) (Grant U54 HG003273