Novel patient-derived xenograft and cell line models for therapeutic testing of pediatric liver cancer.
Journal of Hepatology 65(2):325 (2016)
Pediatric liver cancer is a rare but serious disease whose incidence is rising, and for which the therapeutic options are limited. Development of more targeted, less toxic therapies is hindered by the lack of an experimental animal model that captures the heterogeneity and metastatic capability ...
Current state of pediatric sarcoma biology and opportunities for future discovery: A report from the sarcoma translational research workshop.
Cancer Genetics 209(5):182 (2016)
Sarcomas are a rare subgroup of pediatric cancers comprised of a variety of bone and soft-tissue tumors. While significant advances have been made in improving outcomes of patients with localized pediatric sarcomas since the addition of systemic chemotherapy to local control many decades ago, ou...
Preservation of KIT genotype in a novel pair of patient-derived orthotopic xenograft mouse models of metastatic pediatric CNS germinoma.
Journal of Neuro-Oncology 128(1):47 (2016)
Metastatic intracranial germinoma is difficult to treat. Although the proto-oncogene KIT is recognized as one of the most frequent genetic abnormalities in CNS germinoma, the development of new target therapeutic agents for CNS germinoma is hampered by the lack of clinically-relevant animal mode...
Applications of Genomic Sequencing in Pediatric CNS Tumors.
Oncology (Williston Park, N.Y.) 30(5):411 (2016)
Recent advances in genome-scale sequencing methods have resulted in a significant increase in our understanding of the biology of human cancers. When applied to pediatric central nervous system (CNS) tumors, these remarkable technological breakthroughs have facilitated the molecular characteriza...
Germline Findings in Tumor-Only Sequencing: Points to Consider for Clinicians and Laboratories.
JNCI Journal of the National Cancer Institute 108(4) (2016)
Precision oncology holds great potential to improve patient therapies and outcomes. Tumor sequencing is rapidly moving into clinical care as our understanding of the cancer genome and the availability of targeted therapies increase. Analysis of the cancer genome is most informative when paired w...
When Participants in Genomic Research Grow Up: Contact and Consent at the Age of Majority.
The Journal of Pediatrics 168:226 (2016)
The Pharmacogenomics of Vincristine-Induced Neuropathy: On Pins and Needles.
JAMA Oncology 1(7):975 (2015)
Pediatric Cancer Genetics Research and an Evolving Preventive Ethics Approach for Return of Results after Death of the Subject.
Journal of Law, Medicine & Ethics 43(3):529 (2015)
The return of genetic research results after death in the pediatric setting comes with unique complexities. Researchers must determine which results and through which processes results are returned. This paper discusses the experience over 15 years in pediatric cancer genetics research of return...
BCOR-CCNB3 fusions are frequent in undifferentiated sarcomas of male children.
Modern Pathology 28(4):575 (2015)
The BCOR-CCNB3 fusion gene, resulting from a chromosome X paracentric inversion, was recently described in translocation-negative 'Ewing-like' sarcomas arising in bone and soft tissue. Genetic subclassification of undifferentiated unclassified sarcomas may potentially offer markers for reproduci...
Biological and clinical significance of somatic mutations in Langerhans cell histiocytosis and related histiocytic neoplastic disorders.
ASH Education Program Book 2015(1):559 (2015)
Langerhans cell histiocytosis (LCH), juvenile xanthogranuloma (JXG), and Erdheim-Chester disease (ECD) represent histiocytic disorders with a wide range of clinical manifestations. Until recently, mechanisms of pathogenesis have been speculative and debate has focused on classification of these ...
Recurrent internal tandem duplications of BCOR in clear cell sarcoma of the kidney.
Nature Communications 6:8891 (2015)
The X-linked BCL-6 co-repressor (BCOR) gene encodes a key constituent of a variant polycomb repressive complex (PRC) that is mutated or translocated in human cancers. Here we report on the identification of somatic internal tandem duplications (ITDs) clustering in the C terminus of BCOR in 23 of...
Mutually exclusive recurrent somatic mutations in MAP2K1 and BRAF support a central role for ERK activation in LCH pathogenesis.
Blood 124(19):3007 (2014)
Langerhans cell histiocytosis (LCH) is a myeloproliferative disorder characterized by lesions composed of pathological CD207(+) dendritic cells with an inflammatory infiltrate. BRAFV600E remains the only recurrent mutation reported in LCH. In order to evaluate the spectrum of somatic mutations i...
Clinical tumor sequencing: an incidental casualty of the American College of Medical Genetics and Genomics recommendations for reporting of incidental findings.
Journal of Clinical Oncology 32(21):2203 (2014)
The challenge of informed consent and return of results in translational genomics: empirical analysis and recommendations.
Journal of Law, Medicine & Ethics 42(3):344 (2014)
As exome and genome sequencing move into clinical application, questions surround how to elicit consent and handle potential return of individual genomic results. This study analyzes nine consent forms used in NIH-funded sequencing studies. Content analysis reveals considerable heterogeneity, in...
Obtaining informed consent for clinical tumor and germline exome sequencing of newly diagnosed childhood cancer patients.
Genome Medicine 6(9):69 (2014)
Effectively educating families about the risks and benefits of genomic tests such as whole exome sequencing (WES) offers numerous challenges, including the complexity of test results and potential loss of privacy. Research on best practices for obtaining informed consent (IC) in a variety of cli...
Mutations of PTCH1, MLL2, and MLL3 are not frequent events in hepatoblastoma.
Pediatric Blood & Cancer 58(6):1006 (2012)
Molecular subgroups of medulloblastoma: the current consensus.
Acta Neuropathologica 123(4):465 (2012)
Medulloblastoma, a small blue cell malignancy of the cerebellum, is a major cause of morbidity and mortality in pediatric oncology. Current mechanisms for clinical prognostication and stratification include clinical factors (age, presence of metastases, and extent of resection) as well as histol...
Somatic mutations in the chromatin remodeling gene ARID1A occur in several tumor types.
Human Mutation 33(1):100 (2012)
Mutations in the chromatin remodeling gene ARID1A have recently been identified in the majority of ovarian clear cell carcinomas (OCCCs). To determine the prevalence of mutations in other tumor types, we evaluated 759 malignant neoplasms including those of the pancreas, breast, colon, stomach, l...
The genetic landscape of the childhood cancer medulloblastoma.
Science 331(6016):435 (2011)
Medulloblastoma (MB) is the most common malignant brain tumor of children. To identify the genetic alterations in this tumor type, we searched for copy number alterations using high-density microarrays and sequenced all known protein-coding genes and microRNA genes using Sanger sequencing in a s...
Sodium ion channel mutations in glioblastoma patients correlate with shorter survival.
Molecular Cancer 10:17 (2011)
Glioblastoma Multiforme (GBM) is the most common and invasive astrocytic tumor associated with dismal prognosis. Treatment for GBM patients has advanced, but the median survival remains a meager 15 months. In a recent study, 20,000 genes from 21 GBM patients were sequenced that identified freque...