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Hot Topics of the Day are picked by experts to capture the latest information and publications on public health genomics and precision health for various diseases and health topics. Sources include published scientific literature, reviews, blogs and popular press articles.

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52 hot topic(s) found with the query "Childhood cancer"

Clinical trio genome sequencing facilitates the interpretation of variants in cancer predisposition genes in paediatric tumour patients
C. Shroeder et al, EJHG, July 28, 2023 (Posted: Jul 28, 2023 8AM)

We evaluated clinical trio genome sequencing (TGS) in a cohort of 72 pediatric patients with solid cancers other than retinoblastoma or CNS-tumours. The most prevalent cancer types were sarcoma (n?=?26), neuroblastoma (n?=?15), and nephroblastoma (n?=?10). Overall, P/LP variants in CPS genes were identified in 18.1% of patients (13/72) and P/LP variants in autosomal-dominant CPS genes in 9.7% (7/72). Genetic evaluation would have been recommended for the majority of patients with P/LP variants according to the Jongmans criteria.

Precision Medicine Is Changing the Roles of Healthcare Professionals, Scientists, and Research Staff: Learnings from a Childhood Cancer Precision Medicine Trial
R Daly et al, JPM, June 23, 2023 (Posted: Jun 24, 2023 10AM)

We conducted semi-structured interviews with 85 PRISM professionals from eight professional groups, including oncologists, surgeons, clinical research associates, scientists, genetic professionals, pathologists, animal care technicians, and nurses. We analyzed interviews thematically. Professionals shared that precision medicine can add complexity to their role and result in less certain outcomes for families. Although many participants described experiencing a greater emotional impact from their work, most expressed very positive views about the impact of precision medicine on their profession and its future potential.

Etiology of oncogenic fusions in 5,190 childhood cancers and its clinical and therapeutic implication
Y Liu et al, Nat Comm, April 5, 2023 (Posted: Apr 05, 2023 6AM)

Oncogenic fusions formed through chromosomal rearrangements are hallmarks of childhood cancer that define cancer subtype, predict outcome, persist through treatment, and can be ideal therapeutic targets. However, mechanistic understanding of the etiology of oncogenic fusions remains elusive. Here we report a comprehensive detection of 272 oncogenic fusion gene pairs by using tumor transcriptome sequencing data from 5190 childhood cancer patients.

Diagnostic classification of childhood cancer using multiscale transcriptomics.
Federico Comitani et al. Nature medicine 2023 3 (Posted: Mar 20, 2023 7AM)

In this study, we used an optimized multilevel RNA clustering approach to derive molecular definitions for most childhood cancers. Applying this method to 13,313 transcriptomes, we constructed a pediatric cancer atlas to explore age-associated changes. As a whole, childhood tumors had more transcriptional diversity than adult tumors, maintaining greater expression flexibility. To apply these insights, we designed an ensemble convolutional neural network classifier. We show that this tool was able to match or clarify the diagnosis for 85% of childhood tumors in a prospective cohort.

Assessment of Cancer Predisposition Syndromes in a National Cohort of Children With a Neoplasm.
Jette J Bakhuizen et al. JAMA network open 2023 2 (2) e2254157 (Posted: Feb 04, 2023 7AM)

What is the diagnostic yield of phenotype-driven genetic testing in children with cancer? In this unselected cohort study of 824 Dutch children with a neoplasm, a cancer predisposition syndrome was found in 71 patients (8.6%), of which most (96%) were identified by a phenotype-driven approach.

Heterozygous BRCA1/2 and Mismatch Repair Gene Pathogenic Variants in Children and Adolescents with Cancer.
Kratz Christian P et al. Journal of the National Cancer Institute 2022 8 (Posted: Aug 19, 2022 11AM)

We conducted a meta-analysis of 11 studies that incorporated comprehensive germline testing for children and adolescents with cancer. ClinVar pathogenic/likely pathogenic variants (PVs) in genes of interest were compared to two control groups. Results were validated in a cohort of mainly European cases and controls. Among 3,975 children/adolescents with cancer, significant associations with cancer risk were observed for PVs in BRCA1/2 (26 PVs vs 63 PVs among 27,501 controls, OR 2.78, 95%-CI 1.69—4.45, p<.001) and mismatch repair (MMR) genes (19 PVs vs 14 PVs among 27,501 controls, OR 7.33, 95%-CI 3.64—14.82, p<.001).

Predicting chronic morbidity in childhood cancer survivors.
Vrooman Lynda M et al. Nature medicine 2022 8 (Posted: Aug 09, 2022 7AM)

Approximately 85% of children diagnosed with cancer will be cured of their primary cancer, but epidemiologic and clinical studies have characterized a significant burden of morbidity, as well as excess early mortality, in survivors. Two recent studies show that incorporating genetic factors into risk models improves the prediction of severe obesity for survivors of childhood cancer, which could promote early interventions and better long-term care.

Genetic risk score enhances the risk prediction of severe obesity in adult survivors of childhood cancer.
Sapkota Yadav et al. Nature medicine 2022 7 (Posted: Jul 26, 2022 7AM)

We show the contribution of genetic risk scores (GRSs) to increase prediction of those survivors of childhood cancer who are at risk for severe obesity (body mass index =40?kg?m-2) as an adult. Among 2,548 individuals of European ancestry from the St. Jude Lifetime Cohort Study who were 5-year survivors of childhood cancer, the GRS was found to be associated with 53-fold-higher odds of severe obesity. Addition of GRSs to risk prediction models based on cancer treatment exposures and lifestyle factors significantly improved model prediction (area under the curve increased from 0.68 to 0.75, resulting in the identification of 4.3-times more high-risk survivors).

Genome-wide association studies identify novel genetic loci for epigenetic age acceleration among survivors of childhood cancer
Q Dong et al, Genome Medicine, March 22, 2022 (Posted: Mar 23, 2022 8AM)

Increased epigenetic age acceleration (EAA) in survivors of childhood cancer is associated with specific treatment exposures, unfavorable health behaviors, and presence of certain chronic health conditions. To better understand inter-individual variability, we investigated the genetic basis underlying EAA. We identified novel genetic variants in the SELP gene and HLA region associated with EAA-Horvath and EAA-Hannum, respectively, among survivors of childhood cancer.

Performance of the McGill Interactive Pediatric OncoGenetic Guidelines for Identifying Cancer Predisposition Syndromes.
Goudie Catherine et al. JAMA oncology 2021 10 (Posted: Oct 08, 2021 5AM)

Prompt recognition of a child with a cancer predisposition syndrome (CPS) has implications for cancer management, surveillance, genetic counseling, and cascade testing of relatives. Diagnosis of CPS requires practitioner expertise, access to genetic testing, and test result interpretation. This diagnostic process is not accessible in all institutions worldwide, leading to missed CPS diagnoses. Advances in electronic health technology can facilitate CPS risk assessment.

Comprehensive germline-genomic and clinical profiling in 160 unselected children and adolescents with cancer
R Wagener et al, EJHG< April 12, 2021 (Posted: Apr 12, 2021 8AM)

Through clinical screening, 51 patients (31.3%) were identified as suspicious for an underlying cancer predisposition syndrome (CPS), but only in ten of those patients a pathogenic variant could be identified. In contrast, one patient with a classical CPS and ten patients with prioritized VUS were classified as unremarkable in the clinical work-up. Taken together, a monogenetic causative variant was detected in 13.8% of our patients using WES.

Entering the era of precision medicine in pediatric oncology
D Hadjdadj et al, Nature Medicine, October 19, 2020 (Posted: Oct 19, 2020 0PM)

The Zero Childhood Cancer Program’s multi-platform sequencing approach identified molecular alterations in 94% of a cohort of 247 pediatric patients with high-risk cancers, which has enabled more-precise diagnoses and alternative therapeutic recommendations.

Whole genome, transcriptome and methylome profiling enhances actionable target discovery in high-risk pediatric cancer
M Wong et al, Nature Medicine, October 5, 2020 (Posted: Oct 05, 2020 2PM)

The Zero Childhood Cancer Program is a precision medicine program to benefit children with poor-outcome, rare, relapsed or refractory cancer. Using tumor and germline whole genome sequencing (WGS) and RNA sequencing (RNAseq) across 252 tumors from high-risk pediatric patients with cancer, we identified 968 reportable molecular aberrations.

Precision medicine has a blind spot: children with cancer
G Nichols, StatNews, December 30, 2019 (Posted: Dec 31, 2019 9AM)

Precision medicine, the concept of giving the right treatment to the right patient at the right time, is flourishing in cancer treatment. But there is a blind spot: children are not benefiting enough from the progress we’re making.

Comparative Tumor RNA Sequencing Analysis for Difficult-to-Treat Pediatric and Young Adult Patients With Cancer
OM Vaske et al, JAMA Network Open, October 25, 2019 (Posted: Oct 27, 2019 11AM)

This study suggests that tumor RNA-Seq comparisons may be feasible and highlight the potential clinical utility of incorporating such comparisons into clinical genomic interpretation for difficult-to-treat pediatric and young adult patients with cancer.

Easing the Burden of Children and Families Dealing with Cancer
JE Bloyd, CDC Cancer Blog, October 2019 Brand (Posted: Oct 08, 2019 8AM)

The Promise and the Reality of Genomics to Guide Precision Medicine in Pediatric Oncology: The Decade Ahead.
Evans William E et al. Clinical pharmacology and therapeutics 2019 Sep (Posted: Oct 02, 2019 8AM)

Much has been written about the promise of "precision medicine", especially in oncology, where somatic mutations can influence the response of cancer cells to "targeted therapy". There have been successful examples of targeted therapy improving the outcome of some childhood cancers.

The Childhood Cancer Data Initiative: Transforming the Pediatric Cancer Landscape through Sharing Data
DR Lowy, NCI, August 15, 2019 Brand (Posted: Aug 19, 2019 8AM)

The Childhood Cancer Data Initiative presents a tremendous opportunity—and responsibility—to leverage new technologies for gathering and integrating data and building a framework for easily sharing data among researchers who study pediatric cancer and clinicians who treat our youngest patients with cancer.

Genetics-related service and information needs of childhood cancer survivors and parents: a mixed-methods study
J Vetsch et al, Eur J Hum Genetics, July 30, 2019 (Posted: Jul 31, 2019 10AM)

Genetics in pediatric oncology is becoming increasingly important in diagnostics, treatment and follow-up care. Genetic testing may offer a possibility to stratify survivors follow-up care. However, survivors’ and parents’ preferences and needs for genetics-related services are largely unknown.

Childhood Cancer Data Initiative (CCDI) Symposium
NCI, July 29-31, 2019 Brand (Posted: Jul 30, 2019 8AM)

The NCI Childhood Cancer Data Initiative (CCDI) Symposium: a scientific meeting to gain a common understanding of the current issues and opportunities in childhood cancer research that can be addressed through enhanced data collection and maximum utilization of that data.

Association of Germline BRCA2 Mutations With the Risk of Pediatric or Adolescent Non-Hodgkin Lymphoma.
Wang Zhaoming et al. JAMA oncology 2019 Jul (Posted: Jul 28, 2019 4PM)

The study investigates BRCA2 as a potential predisposition gene for pediatric or adolescent lymphoma, we analyzed 794 additional survivors of lymphoma from the SJLIFE study2 and Childhood Cancer Survivor Study3 cohorts, using whole-genome sequencing data.

The Childhood Cancer Data Initiative: Why Data Sharing Is Essential to Progress
D Lowy, NCI Director Blog, June 12, 2019 Brand (Posted: Jun 12, 2019 10AM)

2019 ASCO: Nearly One-Quarter of Participants in the Pediatric MATCH Trial Have an Actionable Molecular Alteration
by Jo Cavallo, the ASCO Post, May 15, 2019 (Posted: May 16, 2019 8AM)

Molecular Profiling of Hard-to-Treat Childhood and Adolescent Cancers
F Khater et al, JAMA Network Open, April 25, 2019 (Posted: Apr 28, 2019 7AM)

Genetic Profiling May Inform Breast Cancer Risk in Young Childhood Cancer Survivors
AACR News, October 25, 2018 (Posted: Oct 26, 2018 11AM)

Investigation of clinically relevant germline variants detected by next-generation sequencing in patients with childhood cancer: a review of the literature.
Sylvester Dianne E et al. Journal of medical genetics 2018 Oct (Posted: Oct 10, 2018 7AM)

The next frontier in the battle against childhood cancer: Genetics and genomics
N Blanton, Baylor Medicine, Blog, October 9, 2018 (Posted: Oct 09, 2018 1PM)

Finding Pediatric Cancer Genomic Data through PGDI
NCI, September 2018 Brand (Posted: Sep 09, 2018 10AM)

The genomic landscape of pediatric cancers
MassGenomics, Blog Mar 2018 (Posted: Mar 13, 2018 9AM)

Working Toward Greater Precision in Childhood Cancers
NIH Director Blog, Mar 6, 2018 Brand (Posted: Mar 11, 2018 0PM)

Landscapes of childhood tumours
Nature News and Views, Feb 2018 (Posted: Mar 03, 2018 9AM)

Crizotinib Shows Promise for Childhood Cancers
Brand (Posted: Sep 06, 2017 8AM)

NCI-COG Pediatric MATCH trial to test targeted drugs in childhood cancers
NCI, July 2017 Brand (Posted: Jul 27, 2017 7PM)

Recommendations for Childhood Cancer Screening and Surveillance in DNA Repair Disorders.
Walsh Michael F et al. Clinical cancer research : an official journal of the American Association for Cancer Research 2017 Jun 23(11) e23-e31 (Posted: Jun 07, 2017 9AM)

Childhood Cancer Genomics (PDQ®) Health Professional Version
Brand (Posted: Jun 07, 2017 8AM)

Pediatric cancers and precision medicine: The feasibility question
Vector, Boston Children Hospital, February, 2016 (Posted: Feb 08, 2016 9AM)

Genetic sequencing can help guide treatment in children with solid tumors,
Dana-Faber Cancer Institute, January 28, 2016 (Posted: Feb 03, 2016 3PM)

A Quality Improvement Collaborative to Improve Pediatric Primary Care Genetic Services.
Rinke Michael L et al. Pediatrics 2016 Jan (Posted: Feb 03, 2016 3PM)

Recognition of genetic predisposition in pediatric cancer patients: An easy-to-use selection tool.
Jongmans Marjolijn C J et al. European journal of medical genetics 2016 Jan (Posted: Feb 03, 2016 3PM)

Diagnostic Yield of Clinical Tumor and Germline Whole-Exome Sequencing for Children With Solid Tumors
D Williams-Parson et al, JAMA Oncology, January 28, 2016 (Posted: Jan 29, 2016 11AM)

Multicenter Feasibility Study of Tumor Molecular Profiling to Inform Therapeutic Decisions in Advanced Pediatric Solid Tumors- The Individualized Cancer Therapy (iCat) Study
MH Harris et al, JAMA Oncology, January 28, 2016 (Posted: Jan 29, 2016 7AM)

Precision Therapy for Pediatric Cancers
J Khan et al, JAMA Oncology, January 28, 2016 (Posted: Jan 29, 2016 7AM)

Defining Why Cancer Develops in Children
JM Maris, NEJM November 18, 2015 (Posted: Nov 18, 2015 8PM)

Germline Mutations in Predisposition Genes in Pediatric Cancer
J Zhang et al. NEJM, November 18, 2015 (Posted: Nov 18, 2015 7PM)

For Some Children with Cancer, Genomic Information May Help Guide Treatment Decisions
NCI, September 18, 2015 (Posted: Sep 20, 2015 7AM)

Integrative Clinical Sequencing in the Management of Refractory or Relapsed Cancer in Youth
RJ Mody et al. JAMA, September 1, 2015 (Posted: Sep 01, 2015 4PM)

Improving Patient Outcomes With Cancer Genomics Unique Opportunities and Challenges in Pediatric Oncology
RW Schnepp et al. JAMA< September 1, 2015 (Posted: Sep 01, 2015 4PM)

How Can Precision Medicine Help Children With Cancer?
S Ravoori, AACR Blog Post, July 29, 2015 (Posted: Aug 03, 2015 1PM)

Characterising the epigenome as a key component of the fetal exposome in evaluating in utero exposures and childhood cancer risk.
Ghantous Akram et al. Mutagenesis 2015 Feb 26. (Posted: Mar 08, 2015 6PM)

CDC Information: Cancer Prevention Starts in Childhood
Brand (Posted: Feb 25, 2015 0PM)

Obtaining informed consent for clinical tumor and germline exome sequencing of newly diagnosed childhood cancer patients.
Scollon Sarah et al. Genome medicine 2014 (9) 69 (Posted: Feb 12, 2015 8AM)

Precision Medicine Trials for Cancer: A New Era
(Posted: Jan 11, 2014 11AM)

The following is the latest in a series of posts from senior NCI scientists and leaders on NCI?s Annual Plan and Budget Proposal for Fiscal Year 2017, which was officially submitted to the President on September 17, 2015. The proposal provides an overview of NCI?s priorities and key initiatives and the institute?s funding request for the President to consider in formulating his own Fiscal Year (FY) 2017 budget proposal. In this post, Jeff Abrams, M.D., and Nita Seibel, M.D., of NCI's Division of Cancer Treatment and Diagnosis, discuss how precision medicine is influencing the design and conduct of NCI-supported clinical trials. Conventional cancer clinical trials have produced some remarkable results over the past decades, leading to progress against diseases like Hodgkin lymphoma, which was a nearly fatal cancer in adolescents and young adults a half century ago, and breast cancer, which mainly affects adults. However, those trials often required the recruitment of thousands of participants, took up to a decade to complete, and cost hundreds of millions of dollars per trial. Today, with significant advances in genomics, imaging, bioinformatics, and related disciplines, we are designing smaller, quicker, and smarter trials that incorporate the principal tenets of precision medicine. NCI is designing smaller, quicker, and smarter trials that incorporate the principal tenets of precision medicine. Credit: National Human Genome Research Institute In the past 2 years, NCI has launched a series of precision medicine trials, including two lung cancer trials, Lung-MAP and ALCHEMIST, and NCI-MATCH, which is enrolling patients 18 years of age or older with many cancer types, including rare cancers. In 2016, NCI plans to launch a pediatric version of MATCH. All three trials aptly illustrate how precision medicine is influencing how we conduct cancer research. For example, they all include an initial screening step to determine which mutation (or mutations) may be driving an individual patient?s cancer. Next-generation genomic sequencing and analysis is then performed to determine if a patient?s tumor has one or more mutations that align with approved or investigational targeted therapies. This screening step is extremely important because it will be used to determine patient treatment assignment. For example, the screening arm of ALCHEMIST, which is enrolling patients with early-stage non-small cell lung cancer that has been treated surgically, will screen 6,000 to 8,000 patients to determine whether their tumors have mutations in the ALK or EGFR genes. Patients with ALK mutations will be assigned to a clinical trial testing an ALK inhibitor, and those with EGFR mutations will be assigned to a clinical trial testing an EGFR inhibitor. NCI-MATCH also requires a fresh biopsy sample of patients' tumors, which helps to ensure that the sequencing results more accurately reflect the tumor characteristics after exposure to standard treatment, in contrast to samples taken before treatment was given. In addition, because NCI-MATCH has already enrolled nearly 800 patients in just a few months, new enrollments have been halted temporarily while study leaders analyze results from these initial patients. This ?pause? in the trial will allow more mutations and targeted drugs to be added to the trial when it reopens, which will allow NCI-MATCH to address a wider variety of cancer types. Precision medicine trials can also be more nimble than most conventional trials. Both Lung-MAP and ALCHEMIST, for instance, are being amended to include new treatment arms that will assign patients whose tumors lack a mutation to receive immunotherapy drugs. These precision medicine trials present physicians and patients with new issues to consider regarding genetic testing in general. Patients participating in NCI-MATCH and Lung-MAP will be surveyed about their knowledge and preferences regarding genetic testing. It will be important to determine how well patients understand the difference between germline mutations (mutations that can be transmitted to children) and somatic mutations (mutations that are specific to the tumor and are not transmissible to children). We are also making important strides toward applying precision medicine in pediatric trials. The NCI Pediatric MATCH trial will be conducted nationwide and led by NCI and the Children?s Oncology Group (COG). Pediatric MATCH will provide a tremendous opportunity to test molecularly targeted therapies in children and adolescents with recurrent or treatment-resistant solid tumors (including lymphomas)?patients who usually have few other treatment options. Although Pediatric MATCH will be similar to the adult version of NCI-MATCH in design, there will be some differences. The genetic landscape of childhood cancer is far less complex than that of tumors that occur in adults. Childhood tumors contain far fewer genetic mutations than adult tumors, and many mutations that are seen in adult cancers are not detected in pediatric cancers. Therefore, the types of agents included in Pediatric MATCH may differ from those in the adult NCI-MATCH. When interesting results are seen with an agent in Pediatric MATCH, that agent can go on to other trials for its further development. It?s important to stress that not every cancer clinical trial will require such large-scale changes. Large conventional trials still have a valuable role to play, for example, for head-to-head comparisons of therapies with proven efficacy against a specific cancer or cancer subtype, or for testing combinations of therapies. We are already seeing precision medicine trials offer increased flexibility and efficiency, with the potential to more rapidly influence patient care. And as we learn more about how to optimally conduct these trials, our belief is that we will see even more rapid advances in the coming years. Social Media Event We encourage you to leave a comment below with your thoughts and questions about precision oncology trials. We also encourage you to read the Annual Plan and Budget Proposal and the remaining blog posts in this series. Cancer

Disclaimer: Articles listed in Hot Topics of the Day are selected by Public Health Genomics Branch to provide current awareness of the scientific literature and news. Inclusion in the update does not necessarily represent the views of the Centers for Disease Control and Prevention nor does it imply endorsement of the article's methods or findings. CDC and DHHS assume no responsibility for the factual accuracy of the items presented. The selection, omission, or content of items does not imply any endorsement or other position taken by CDC or DHHS. Opinion, findings and conclusions expressed by the original authors of items included in the Clips, or persons quoted therein, are strictly their own and are in no way meant to represent the opinion or views of CDC or DHHS. References to publications, news sources, and non-CDC Websites are provided solely for informational purposes and do not imply endorsement by CDC or DHHS.