Genomes for Kids: The Scope of Pathogenic Mutations in Pediatric Cancer Revealed by Comprehensive DNA and RNA Sequencing.

Unlabelled: Genomic studies of pediatric cancer have primarily focused on specific tumor types or high-risk disease. Here, we used a three-platform sequencing approach, including whole-genome sequencing (WGS), whole-exome sequencing (WES), and RNA sequencing (RNA-seq), to examine tumor and germline genomes from 309 prospectively identified children with newly diagnosed (85%) or relapsed/refractory (15%) cancers, unselected for tumor type. Eighty-six percent of patients harbored diagnostic (53%), prognostic (57%), therapeutically relevant (25%), and/or cancer-predisposing (18%) variants.

Knowledge Is Power: Benefits, Risks, Hopes, and Decision-Making Reported by Parents Consenting to Next-Generation Sequencing for Children and Adolescents with Cancer.

Objectives: To qualitatively describe parent perspectives of next-generation genomic sequencing (NGS) for their children with cancer, including perceived benefits, risks, hopes/expectations, and decision-making process when consenting or not consenting to NGS and prior to result disclosure.

Data Sources: Qualitative interviews were used.

Conclusion: Altruism is an important factor in parents consenting to NGS testing, as well as making sense of their child's cancer and legacy building.

Creating a cancer genomics curriculum for pediatric hematology-oncology fellows: A national needs assessment.

Background: With the advent of next generation sequencing, tumor and germline genomic testing are increasingly being used in the management of pediatric cancer patients. Despite this increase in testing, many pediatric hematology-oncology (PHO) providers are not confident interpreting or utilizing tumor or germline genomic results to care for their patients.

Methods: We developed and delivered a needs assessment survey to PHO program directors, attendings, and fellows in the United States to understand this deficiency, gather data on existing cancer genomics educational initiatives, and query preferences for creating a future curriculum.

Amphotericin B Penetrates into the Central Nervous System Through Focal Disruption of the Blood Brain Barrier in Experimental Hematogenous Meningoencephalitis.

Hematogenous meningoencephalitis (HCME) is a life-threatening complication of neonates and immunocompromised children. Amphotericin B (AmB) shows poor permeability and low cerebrospinal fluid (CSF) concentrations, but is effective in treatment of HCME. In order to better understand the mechanism of CNS penetration of AmB, we hypothesized that AmB may achieve focally higher concentrations in infected CNS lesions.

Speaking genomics to parents offered germline testing for cancer predisposition: Use of a 2-visit consent model.

Background: Patients with cancer are increasingly offered genomic sequencing, including germline testing for cancer predisposition or other disorders. Such testing is unfamiliar to patients and families, and clear communication is needed to introduce genomic concepts and convey risk and benefit information.

Methods: Parents of children with cancer were offered the opportunity to have their children's tumor and germline examined with clinical genomic sequencing.

Parent-child communication surrounding genetic testing for Li-Fraumeni syndrome: Living under the cloud of cancer.

Background: Advances in the application of genetic technologies reveal a growing number of heritable disorders associated with an increased risk to develop cancer during childhood. As genetic testing is increasingly employed in the clinical setting, it is essential to understand whether parents communicate with their children about test results and to elucidate the factors that influence the content and outcomes of these conversations.

Methods: Semistructured interviews were conducted with 14 parents whose children tested positive for Li-Fraumeni syndrome (LFS).

Ethical considerations surrounding germline next-generation sequencing of children with cancer.

The advent of next-generation sequencing (NGS) has introduced an exciting new era in biomedical research. NGS forms the foundation of current genetic testing approaches, including targeted gene panel testing, as well as more comprehensive whole-exome and whole-genome sequencing. Together, these approaches promise to provide critical insights into the understanding of health and disease.

Integrating next-generation sequencing into pediatric oncology practice: An assessment of physician confidence and understanding of clinical genomics.

Background: The incorporation of genomic testing to identify targetable somatic alterations and predisposing germline mutations into the clinical setting is becoming increasingly more common. Despite its potential usefulness, to the authors' knowledge physician confidence with regard to understanding and applying genomic testing remains unclear, particularly within the realm of pediatric oncology.

Methods: Before initiating an institutional feasibility study regarding the integration of clinical genomic testing, the authors surveyed pediatric oncologists regarding their confidence around understanding of genomic testing, perceived usefulness of test results, preferences around the disclosure of germline test results, and possible risks and benefits of testing.

Li-Fraumeni syndrome: a paradigm for the understanding of hereditary cancer predisposition.

Li-Fraumeni syndrome (LFS) is a rare cancer predisposing condition caused by germline mutations in TP53, the gene encoding the TP53 transcription factor. LFS is typified by the development of a wide spectrum of childhood and adult-onset malignancies, which includes, among others, the lymphoid and myeloid leukaemias, myelodysplastic syndrome and, to a lesser extent, lymphoma. Accordingly, it is important that haematologists/oncologists be familiar with this pleiotropic hereditary cancer syndrome.

Decreased infection-related mortality and improved survival in severe aplastic anemia in the past two decades.

Background: Persistent neutropenia associated with severe aplastic anemia (SAA) is an important risk factor for development of life-threatening infections. Earlier studies underscored the high mortality associated with invasive fungal infections (IFIs) in SAA. However, little is known about the current patterns of infections and the impact of advances in anti-infective therapy on survival in SAA.

Infections in patients with aplastic anemia.

Infection is a major cause of death in patients with aplastic anemia (AA). There are differences between the immunocompromised state of a patient with AA and the patient who is neutropenic due to chemotherapy and this leads to a difference in the infections that they incur. Prolonged neutropenia is one of the largest risk factors for the development of infections with the invasive mycoses and bacteria.

Trans fatty acids and conjugated linoleic acids in the milk of urban women and nomadic Fulani of northern Nigeria.

Background: Trans fatty acids (TFAs) and conjugated linoleic acids (CLAs) are present in dairy products and human milk and can have detrimental and beneficial effects in humans. The content of TFAs and CLAs in milk is determined largely by the diet of the mother.

Methods: We compared the proportions of TFAs and CLAs in the milk of rural Fulani in northern Nigeria who consume dairy products to that of women living in an urban center who consume little in the way of dairy products.