The Pediatric Cancer Genome Project

Subject terms: Cancer genomics• Paediatric cancer• Sequencing At a glance Figures View all figures Figure 1: Frequency of cancer diagnoses and leukemia subtypes in children and adults. (a) The frequency of cancer types in children (left) and adults (right) on the basis of 2012 Surveillance, Epidemiology and End Results (SEER) data. Each chart is organized with cancers listed from the most common to the least common in a clockwise fashion. (b) The frequency of T-cell lineage (blue text) and B-cell lineage (black text) subtypes of acute lymphoblastic leukemia (ALL) in children (left) and adults (right). Each chart is organized with ALL subtypes listed from the most common to the least common in a clockwise fashion. iAMP21, intrachromosomal amplification of chromosome 21. Full size image View in article Figure 2: Genetic landscape of 15 different types of pediatric cancers determined from whole-genome sequencing of 260 tumors and matching germline samples. The number of somatic mutations in each sample, including single-nucleotide variations (SNVs), insertion and/or deletion events (indels) and structural variations, is shown as the height in the three-dimensional graph. Only high-quality variations or validated somatic mutations are included in the summary. CDS, protein-coding regions; tier 1, mutations in annotated genes; tier 2, mutations in non-coding conserved or regulatory regions; tier 3, mutations in non-repetitive, non-coding and non-conserved regions; tier 4, mutations in repetitive regions. Tier 2 and tier 3/tier 4 mutations were rescaled to 1/10 and 1/100 of the original counts to maintain a consistent scale with the results for other somatic lesions. INF, infant ALL; CBF, core-binding-factor acute myeloid leukemia; TALL, T-cell ALL; AMLM7, acute megakaryoblastic leukemia; HYPO, hypodiploid ALL; PHALL, Philadelphia chromosome–positive BCR-ABL1 ALL; RB, retinoblastoma; RHB, rhabdomyosarcoma; NBL, neuroblastoma; OS, osteosarcoma; ACT, adrenocortical carcinoma; HGG, high-grade glioblastoma; LGG, low-grade glioma; EPD, ependymoma; MB, medulloblastoma. Full size image View in article

[1]  R. Arceci.  Evolution of human BCR–ABL1 lymphoblastic leukaemia-initiating cells , 2011 .

[2]  D. Altshuler,et al.  A map of human genome variation from population-scale sequencing , 2010, Nature.

[3]  Matthew W. Wilson,et al.  A Novel Retinoblastoma Therapy from Genomic and Epigenetic Analyses , 2011, Nature.

[4]  Bin Tean Teh,et al.  Somatic mutations of the histone H3K27 demethylase, UTX, in human cancer , 2009, Nature Genetics.

[5]  Ching-Hon Pui,et al.  Challenging issues in pediatric oncology , 2011, Nature Reviews Clinical Oncology.

[6]  Li Ding,et al.  Somatic Histone H3 Alterations in Paediatric Diffuse Intrinsic Pontine Gliomas and Non-Brainstem Glioblastomas , 2012, Nature Genetics.

[7]  D. Busam,et al.  An Integrated Genomic Analysis of Human Glioblastoma Multiforme , 2008, Science.

[8]  Kiran C. Bobba,et al.  The genetic basis of early T-cell precursor acute lymphoblastic leukaemia , 2012, Nature.

[9]  Paul Medvedev,et al.  Computational methods for discovering structural variation with next-generation sequencing , 2009, Nature Methods.

[10]  Kenneth H. Buetow,et al.  CREBBP mutations in relapsed acute lymphoblastic leukaemia , 2011, Nature.

[11]  C. Pui,et al.  Lessons from the past: Opportunities to improve childhood cancer survivor care through outcomes investigations of historical therapeutic approaches for pediatric hematological malignancies , 2012, Pediatric blood & cancer.

[12]  Michael C. Rusch,et al.  CREST maps somatic structural variation in cancer genomes with base-pair resolution , 2011, Nature Methods.

[13]  Jinghui Zhang,et al.  Association of age at diagnosis and genetic mutations in patients with neuroblastoma. , 2012, JAMA.

[14]  James R. Downing,et al.  Genomic Analysis of the Clonal Origins of Relapsed Acute Lymphoblastic Leukemia , 2008, Science.

[15]  J. Uhm.  Comprehensive genomic characterization defines human glioblastoma genes and core pathways , 2009 .

[16]  William Stafford Noble,et al.  Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project , 2007, Nature.

[17]  Andrew Menzies,et al.  The patterns and dynamics of genomic instability in metastatic pancreatic cancer , 2010, Nature.

[18]  M. Nowak,et al.  Distant Metastasis Occurs Late during the Genetic Evolution of Pancreatic Cancer , 2010, Nature.

[19]  A. Jemal,et al.  Cancer statistics, 2012 , 2012, CA: a cancer journal for clinicians.

[20]  David T. W. Jones,et al.  Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma , 2012, Nature.