1. Novel patient-derived xenograft and cell line models for therapeutic testing of pediatric liver cancer.

    Journal of Hepatology 65(2):325 (2016) PMID 27117591

    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 ...
  2. Genomic Profiling of Pediatric Acute Myeloid Leukemia Reveals a Changing Mutational Landscape from Disease Diagnosis to Relapse.

    Cancer Research 76(8):2197 (2016) PMID 26941285 PMCID PMC4873364

    The genomic and clinical information used to develop and implement therapeutic approaches for acute myelogenous leukemia (AML) originated primarily from adult patients and has been generalized to patients with pediatric AML. However, age-specific molecular alterations are becoming more evident a...
  3. Ampullary Cancers Harbor ELF3 Tumor Suppressor Gene Mutations and Exhibit Frequent WNT Dysregulation.

    Cell Reports 14(4):907 (2016) PMID 26804919 PMCID PMC4982376

    The ampulla of Vater is a complex cellular environment from which adenocarcinomas arise to form a group of histopathologically heterogenous tumors. To evaluate the molecular features of these tumors, 98 ampullary adenocarcinomas were evaluated and compared to 44 distal bile duct and 18 duodenal ...
  4. ITD assembler: an algorithm for internal tandem duplication discovery from short-read sequencing data.

    BMC Bioinformatics 17:188 (2016) PMID 27121965 PMCID PMC4847212

    Detection of tandem duplication within coding exons, referred to as internal tandem duplication (ITD), remains challenging due to inefficiencies in alignment of ITD-containing reads to the reference genome. There is a critical need to develop efficient methods to recover these important mutation...
  5. Recurrent DGCR8, DROSHA, and SIX homeodomain mutations in favorable histology Wilms tumors.

    Cancer Cell 27(2):286 (2015) PMID 25670082 PMCID PMC4800737

    We report the most common single-nucleotide substitution/deletion mutations in favorable histology Wilms tumors (FHWTs) to occur within SIX1/2 (7% of 534 tumors) and microRNA processing genes (miRNAPGs) DGCR8 and DROSHA (15% of 534 tumors). Comprehensive analysis of 77 FHWTs indicates that tumor...
  6. Initial testing (stage 1) of the PARP inhibitor BMN 673 by the pediatric preclinical testing program: PALB2 mutation predicts exceptional in vivo response to BMN 673.

    Pediatric Blood & Cancer 62(1):91 (2015) PMID 25263539 PMCID PMC4456187

    BMN 673 is a potent inhibitor of poly-ADP ribose polymerase (PARP) that is in clinical testing with a primary focus on BRCA-mutated cancers. BMN 673 is active both through inhibiting PARP catalytic activity and by tightly trapping PARP to DNA at sites of single strand breaks. BMN 673 was tested ...
  7. Assessing structural variation in a personal genome-towards a human reference diploid genome.

    BMC Genomics 16:286 (2015) PMID 25886820 PMCID PMC4490614

    Characterizing large genomic variants is essential to expanding the research and clinical applications of genome sequencing. While multiple data types and methods are available to detect these structural variants (SVs), they remain less characterized than smaller variants because of SV diversity...
  8. Recurrent internal tandem duplications of BCOR in clear cell sarcoma of the kidney.

    Nature Communications 6:8891 (2015) PMID 26573325 PMCID PMC4660214

    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...
  9. Rise and fall of subclones from diagnosis to relapse in pediatric B-acute lymphoblastic leukaemia.

    Nature Communications 6:6604 (2015) PMID 25790293 PMCID PMC4377644

    There is incomplete understanding of genetic heterogeneity and clonal evolution during cancer progression. Here we use deep whole-exome sequencing to describe the clonal architecture and evolution of 20 pediatric B-acute lymphoblastic leukaemias from diagnosis to relapse. We show that clonal div...
  10. MLLT1 YEATS domain mutations in clinically distinctive Favourable Histology Wilms tumours.

    Nature Communications 6:10013 (2015) PMID 26635203 PMCID PMC4686660

    Wilms tumour is an embryonal tumour of childhood that closely resembles the developing kidney. Genomic changes responsible for the development of the majority of Wilms tumours remain largely unknown. Here we identify recurrent mutations within Wilms tumours that involve the highly conserved YEAT...
  11. Mutually exclusive recurrent somatic mutations in MAP2K1 and BRAF support a central role for ERK activation in LCH pathogenesis.

    Blood 124(19):3007 (2014) PMID 25202140 PMCID PMC4224195

    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...
  12. Long-range massively parallel mate pair sequencing detects distinct mutations and similar patterns of structural mutability in two breast cancer cell lines.

    Cancer Genetics 204(8):447 (2011) PMID 21962895 PMCID PMC3185296

    Cancer genomes frequently undergo genomic instability resulting in accumulation of chromosomal rearrangement. To date, one of the main challenges has been to confidently and accurately identify these rearrangements by using short-read massively parallel sequencing. We were able to improve cancer...
  13. A sequence-level map of chromosomal breakpoints in the MCF-7 breast cancer cell line yields insights into the evolution of a cancer genome.

    Genome Research 19(2):167 (2009) PMID 19056696 PMCID PMC2652200

    By applying a method that combines end-sequence profiling and massively parallel sequencing, we obtained a sequence-level map of chromosomal aberrations in the genome of the MCF-7 breast cancer cell line. A total of 157 distinct somatic breakpoints of two distinct types, dispersed and clustered,...