Dataset Information

Genomic Features and Clinical Characteristics of Adolescents and Young Adults With Cholangiocarcinoma.

ABSTRACT: Background: Adolescents and young adults (AYAs) diagnosed with cancer between ages 15 and 45 years may exhibit unique biologic and genomic characteristics as well as clinical features, resulting in differences in clinical characters and drug resistance. However, compared to other solid cancers, relatively few studies have been conducted in this age group in cholangiocarcinoma (CCA). This study is performed to investigate the clinical and molecular features of AYAs with CCA. Methods: Three cohorts, including the external dataset (TCGA and MSKCC) and the perihilar CCA databank of Chinese tertiary hospitals, were contained in this study. Pathway and process enrichment analysis had been carried out with the following ontology sources: KEGG Pathway, GO Biological Processes, Reactome Gene Sets, Canonical Pathways, and CORUM. Metascape and GEPIA datasets were used for bioinformatic analysis. P < 0.05 was considered statistically significant. All statistical analyses were performed with GraphPad Prism (version 7.0; GraphPad Software, La Jolla, California) and R studio (version 3.6.1; R studio, Boston, Massachusetts). Results: Compared to older adults, AYAs with CCA presented with worse overall survival, although the difference was not significant. Specific to patients with stage IV CCAs who underwent chemotherapy, AYAs were associated with significantly poorer overall survival (OS) (p = 0.03, hazards ratio (HR) 3.01, 95% confidence interval (CI) 1.14-4.91). From the anatomical perspective, more extrahepatic CCA was detected in the AYA group. Microsatellite instability (MSI) occurred in 3% of older patients in the present study. Nevertheless, none of the AYAs had MSI status. In this study, AYAs gained an enhanced frequency of additional sex combs like 1 (ASXL1) (p = 0.02) and KMT2C (p = 0.02) mutation than their older counterparts. Besides ASXL1 and KMT2C, the genes enriched in AYAs with CCA were analyzed by pathway and process enrichment analysis. And those genes were found to be associated with poorer differentiation, deubiquitination, and WNT signal pathway. Moreover, AYAs were relevant to poor differentiation and advanced tumor stage. Conclusion: This study offered a preliminary landscape of the clinical and molecular features of early-onset biliary cancers. Further studies including more samples are essential to investigate whether ASXL1 and KMT2C could be considered as potentially targetable genomic signatures for young patients.

SUBMITTER: Feng H

PROVIDER: S-EPMC6971196 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Genomic Features and Clinical Characteristics of Adolescents and Young Adults With Cholangiocarcinoma.

Feng Hao H Tong Huan H Yan Jiayan J He Min M Chen Wei W Wang Jian J

Frontiers in oncology 20200114

<b>Background:</b> Adolescents and young adults (AYAs) diagnosed with cancer between ages 15 and 45 years may exhibit unique biologic and genomic characteristics as well as clinical features, resulting in differences in clinical characters and drug resistance. However, compared to other solid cancers, relatively few studies have been conducted in this age group in cholangiocarcinoma (CCA). This study is performed to investigate the clinical and molecular features of AYAs with CCA. <b>Methods:</b ...[more]

PMID: 32010606

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Project description:BackgroundColorectal cancer is extremely rare in childhood. Published case series reporting children and adolescents with colorectal cancer have not focused on the underlying genetic aspects of the tumour or genetic susceptibility of the families.AimsWe examined a cohort of patients with early onset colorectal cancer to determine whether a specific genetic predisposition could be elucidated. In particular, we focused on whether DNA mismatch repair gene deficiency which causes hereditary non-polyposis colorectal cancer (HNPCC) could be elucidated.MethodsPatients with colorectal cancer </=24 years of age were identified from a database at the Familial Gastrointestinal Cancer Registry at Mount Sinai Hospital, Toronto. Detailed pedigrees were ascertained from the proband or parents. Tumours were tested for microsatellite instability, a hallmark of HNPCC. Germline mismatch repair gene mutations (MSH2 and MLH1) were sought in some cases. Clinical data were obtained by chart audit.ResultsAmong 1382 probands in our registry, 16 (1%) colorectal cancer patients were 24 years or younger at the time of diagnosis. Microsatellite instability was identified in tumours from eight (73%) of 11 evaluated patients. Germline mutations in mismatch repair genes were identified in six of 12 patients, including MSH2 (n = 3), MLH1 (n = 2), and PMS2 (n = 1). Ten (63%) of 16 families met the Amsterdam criteria for HNPCC. Among these, six were screened for mismatch repair gene mutations and three were found to carry MSH2 or MLH1 germline mutations. Location of the colorectal cancers included rectum/sigmoid (n = 9), splenic flexure (n = 2), hepatic flexure (n = 3), and caecum (n = 2). Forty four per cent (7/16) of these young cases developed additional malignancies (gastrointestinal (n = 8) and extraintestinal (n = 4)) during follow up (mean 12.8 (SD 12.4) years (range 0.08-30)).ConclusionsPatients with early onset colorectal carcinoma often have an inherited predisposition to the disease. Tumours with high frequency microsatellite instability and germline mutations of mismatch repair genes are sufficiently common in this patient population that they should be considered, even though family histories may not satisfy the stringent Amsterdam criteria for HNPCC. Young colorectal cancer patients are at increased risk of developing second gastrointestinal and extraintestinal malignancies.

Project description:BackgroundTo protect minors' future autonomy, professional organizations have historically discouraged returning predictive adult-onset genetic test results and carrier status to children. Recent clinical guidance diverges from this norm, suggesting that when minors have genomic sequencing performed for clinical purposes, parents and children should have the opportunity to learn secondary findings, including for some adult-onset conditions. While parents can currently opt in or out of receiving their child's secondary findings, the American Society of Human Genetics Workgroup on Pediatric Genetic and Genomic Testing suggests including adolescents in the decision-making process. However, it is not clear what factors young people consider when given the opportunity to learn genetic findings for themselves. We are examining adolescents', young adults', and parents' (if applicable) decisions about learning genomic information for the adolescent.MethodsWe are enrolling assenting (ages 13-17) adolescents and consenting (ages 18-21) young adults in a prospective genomic screening study to assess the choices they make about receiving individual genomic results. Participants use an online tool to indicate whether they want to learn their personal genetic risk for specific preventable, treatable, and adult-onset conditions, as well as carrier status for autosomal recessive conditions. We are examining 1) how choices differ between adolescent and young adult cohorts (as well as between adolescents/young adults and parents) and 2) decisional conflict and stability across study timepoints. Results are returned based on participants' choices. Qualitative interviews with a subset of participants explore decisional stability, adolescent/young adult engagement with parents in decision-making, and the impact of learning pathogenic/likely pathogenic and carrier results.DiscussionThis study explores decision making and decision stability between adolescents and parents (where applicable), as well as the ethical implications and impact of return of clinical-grade genetic research results to adolescents and young adults. The results of this study will contribute empirical evidence to support best practices and guidance on engaging young people in genetic research studies and clinical care that offer return of results.

Project description:IntroductionCigarette advertising is a causal agent of smoking uptake among young people. Although prior research links ad receptivity to tobacco product interest and use, little is known regarding the specific advertising tactics associated with increased product appeal among young people.MethodsA national sample of 13-20 year-olds (N = 3688, youth) and 21-24 year-olds (N = 1556, young adults) in the US participated in an online survey in 2017 (mean age 18.1 years). The majority (72.0%) of youth and nearly half (44.8%) of young adults were never smokers. Participants were shown a cigarette ad, randomly assigned from a pool of 50 advertisements, and reported how much they liked the ad, and were curious about and interested in using the advertised product. All 50 advertisements were content analyzed for a variety of features. Data from the survey and content analysis were merged and mixed effects analyses used to identify the features associated with increased liking, curiosity, and interest in using, referred to collectively as product appeal.ResultsPresence of a sweepstakes offer was associated with increased liking, curiosity and interest among youth and curiosity and interest among young adults. Outdoors settings, flora imagery, natural descriptors, and environmental themes were associated with increased appeal. Price reductions (eg, coupons) were associated with decreased appeal among youth.ConclusionsThis study identified several advertising tactics associated with increased appeal among youth and young adults. If additional research confirms these findings, the U.S. Food and Drug Association should consider restricting use of these tactics in tobacco advertising.ImplicationsThis study's findings provide insight into features of cigarette ads that appeal to youth and young adults. Overall, the presence of sweepstakes appealed to youth and young adults and outdoors and environmental themes were particularly appealing to young adults. Such tactics could serve to further brand engagement, improve brand image and lead to initiation or escalation of use. If confirmatory studies further demonstrate the effects of the tactics identified in this study on youth product appeal, U.S. Food and Drug Administration should consider using its authority to restrict the use of youth-appealing tactics.

Dataset Information

Genomic Features and Clinical Characteristics of Adolescents and Young Adults With Cholangiocarcinoma.

Publications

Genomic Features and Clinical Characteristics of Adolescents and Young Adults With Cholangiocarcinoma.

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