Pui, C.H. et al. Treating childhood acute lymphoblastic leukemia without cranial irradiation. N. Engl. J. Med. 360, 2730–2741 (2009).
Kuiper, R.P. et al. High-resolution genomic profiling of childhood ALL reveals novel recurrent genetic lesions affecting pathways involved in lymphocyte differentiation and cell cycle progression. Leukemia 21, 1258–1266 (2007).
Mullighan, C.G. et al. Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. Nature 446, 758–764 (2007).
Kuiper, R.P. et al. IKZF1 deletions predict relapse in uniformly treated pediatric precursor B-ALL. Leukemia 24, 1258–1264 (2010).
Mullighan, C.G. et al. Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia. N. Engl. J. Med. 360, 470–480 (2009).
Mullighan, C.G. et al. CREBBP mutations in relapsed acute lymphoblastic leukaemia. Nature 471, 235–239 (2011).
Harrison, C.J. et al. Three distinct subgroups of hypodiploidy in acute lymphoblastic leukaemia. Br. J. Haematol. 125, 552–559 (2004).
Heerema, N.A. et al. Hypodiploidy with less than 45 chromosomes confers adverse risk in childhood acute lymphoblastic leukemia: a report from the children's cancer group. Blood 94, 4036–4045 (1999).
Nachman, J.B. et al. Outcome of treatment in children with hypodiploid acute lymphoblastic leukemia. Blood 110, 1112–1115 (2007).
Raimondi, S.C. et al. Reassessment of the prognostic significance of hypodiploidy in pediatric patients with acute lymphoblastic leukemia. Cancer 98, 2715–2722 (2003).
Raimondi, S.C. Cytogenetics of acute leukemias. in Childhood Leukemias (ed. Pui, C.H.) (Cambridge University Press, 2012).
Carroll, A.J. et al. Masked hypodiploidy: hypodiploid acute lymphoblastic leukemia (ALL). in Children mimicking hyperdiploid ALL: a report from the Children's Oncology Group (COG) AALL03B1 study. Blood: ASH Annual Meeting Abstracts 114, 1580 (2009).
Li, F.P. & Fraumeni, J.F. Jr. Soft-tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome? Ann. Intern. Med. 71, 747–752 (1969).
Malkin, D. Li-Fraumeni syndrome. Genes Cancer 2, 475–484 (2011).
Zhang, J. et al. The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature 481, 157–163 (2012).
Xu, G.F. et al. The neurofibromatosis type 1 gene encodes a protein related to GAP. Cell 62, 599–608 (1990).
Cawthon, R.M. et al. A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations. Cell 62, 193–201 (1990).
Viskochil, D. et al. Deletions and a translocation interrupt a cloned gene at the neurofibromatosis type 1 locus. Cell 62, 187–192 (1990).
Wallace, M.R. et al. Type 1 neurofibromatosis gene: identification of a large transcript disrupted in three NF1 patients. Science 249, 181–186 (1990).
Side, L.E. et al. Mutations of the NF1 gene in children with juvenile myelomonocytic leukemia without clinical evidence of neurofibromatosis, type 1. Blood 92, 267–272 (1998).
Balgobind, B.V. et al. Leukemia-associated NF1 inactivation in patients with pediatric T-ALL and AML lacking evidence for neurofibromatosis. Blood 111, 4322–4328 (2008).
McLendon, R. et al. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455, 1061–1068 (2008).
Klopfenstein, K.J., Sommer, A. & Ruymann, F.B. Neurofibromatosis-Noonan syndrome and acute lymphoblastic leukemia: a report of two cases. J. Pediatr. Hematol. Oncol. 21, 158–160 (1999).
Stiller, C.A., Chessells, J.M. & Fitchett, M. Neurofibromatosis and childhood leukaemia/lymphoma: a population-based UKCCSG study. Br. J. Cancer 70, 969–972 (1994).
Messiaen, L. et al. Mosaic type-1 NF1 microdeletions as a cause of both generalized and segmental neurofibromatosis type-1 (NF1). Hum. Mutat. 32, 213–219 (2011).
Marculescu, R. et al. Recombinase, chromosomal translocations and lymphoid neoplasia: targeting mistakes and repair failures. DNA Repair (Amst.) 5, 1246–1258 (2006).
Mullighan, C.G. et al. BCR-ABL1 lymphoblastic leukaemia is characterized by the deletion of Ikaros. Nature 453, 110–114 (2008).
Kohno, S., Minowada, J. & Sandberg, A.A. Chromosome evolution of near-haploid clones in an established human acute lymphoblastic leukemia cell line (NALM-16). J. Natl. Cancer Inst. 64, 485–493 (1980).
Kratz, C.P. et al. The mutational spectrum of PTPN11 in juvenile myelomonocytic leukemia and Noonan syndrome/myeloproliferative disease. Blood 106, 2183–2185 (2005).
Tartaglia, M. et al. Diversity and functional consequences of germline and somatic PTPN11 mutations in human disease. Am. J. Hum. Genet. 78, 279–290 (2006).
De Filippi, P. et al. Germ-line mutation of the NRAS gene may be responsible for the development of juvenile myelomonocytic leukaemia. Br. J. Haematol. 147, 706–709 (2009).
Matsuda, K. et al. Spontaneous improvement of hematologic abnormalities in patients having juvenile myelomonocytic leukemia with specific RAS mutations. Blood 109, 5477–5480 (2007).
Kawabuchi, M. et al. Transmembrane phosphoprotein Cbp regulates the activities of Src-family tyrosine kinases. Nature 404, 999–1003 (2000).
Brdicka, T. et al. Phosphoprotein associated with glycosphingolipid-enriched microdomains (PAG), a novel ubiquitously expressed transmembrane adaptor protein, binds the protein tyrosine kinase csk and is involved in regulation of T cell activation. J. Exp. Med. 191, 1591–1604 (2000).
Davidson, D., Bakinowski, M., Thomas, M.L., Horejsi, V. & Veillette, A. Phosphorylation-dependent regulation of T-cell activation by PAG/Cbp, a lipid raft-associated transmembrane adaptor. Mol. Cell. Biol. 23, 2017–2028 (2003).
Zhang, S.Q. et al. Shp2 regulates SRC family kinase activity and Ras/Erk activation by controlling Csk recruitment. Mol. Cell 13, 341–355 (2004).
Kalland, M.E., Solheim, S.A., Skanland, S.S., Tasken, K. & Berge, T. Modulation of proximal signaling in normal and transformed B cells by transmembrane adapter Cbp/PAG. Exp. Cell Res. 318, 1611–1619 (2012).
Imamura, J., Miyoshi, I. & Koeffler, H.P. p53 in hematologic malignancies. Blood 84, 2412–2421 (1994).
Zhang, J. et al. Key pathways are frequently mutated in high-risk childhood acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood 118, 3080–3087 (2011).
Petitjean, A. et al. Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: Lessons from recent developments in the IARC TP53 database. Hum. Mutat. 6, 622–629 (2007).
Cho, Y., Gorina, S., Jeffrey, P.D. & Pavletich, N.P. Crystal structure of a p53 tumor suppressor-DNA complex: understanding tumorigenic mutations. Science 265, 346–355 (1994).
Hof, J. et al. Mutations and deletions of the TP53 gene predict nonresponse to treatment and poor outcome in first relapse of childhood acute lymphoblastic leukemia. J. Clin. Oncol. 29, 3185–93 (2011).
Wattel, E. et al. p53 mutations are associated with resistance to chemotherapy and short survival in hematologic malignancies. Blood 84, 3148–3157 (1994).
Rovinski, B. & Benchimol, S. Immortalization of rat embryo fibroblasts by the cellular p53 oncogene. Oncogene 2, 445–452 (1988).
el-Deiry, W.S. et al. WAF1, a potential mediator of p53 tumor suppression. Cell 75, 817–825 (1993).
Rebollo, A. & Schmitt, C. Ikaros, Aiolos and Helios: transcription regulators and lymphoid malignancies. Immunol. Cell Biol. 81, 171–175 (2003).
Georgopoulos, K. et al. The Ikaros gene is required for the development of all lymphoid lineages. Cell 79, 143–156 (1994).
Wang, J.H. et al. Selective defects in the development of the fetal and adult lymphoid system in mice with an Ikaros null mutation. Immunity 5, 537–549 (1996).
Kim, J. et al. Ikaros DNA-binding proteins direct formation of chromatin remodeling complexes in lymphocytes. Immunity 10, 345–355 (1999).
Thornton, A.M. et al. Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells. J. Immunol. 184, 3433–3441 (2010).
Getnet, D. et al. A role for the transcription factor Helios in human CD4+CD25+ regulatory T cells. Mol. Immunol. 47, 1595–1600 (2010).
Sugimoto, N. et al. Foxp3-dependent and -independent molecules specific for CD25+CD4+ natural regulatory T cells revealed by DNA microarray analysis. Int. Immunol. 18, 1197–1209 (2006).
Hahm, K. et al. Helios, a T cell-restricted Ikaros family member that quantitatively associates with Ikaros at centromeric heterochromatin. Genes Dev. 12, 782–796 (1998).
Kelley, C.M. et al. Helios, a novel dimerization partner of Ikaros expressed in the earliest hematopoietic progenitors. Curr. Bio. 8, 508–15 (1998).
Goodman, R.H. & Smolik, S. CBP/p300 in cell growth, transformation, and development. Genes Dev. 14, 1553–1577 (2000).
Kasper, L.H. et al. Two transactivation mechanisms cooperate for the bulk of HIF-1-responsive gene expression. EMBO J. 24, 3846–3858 (2005).
Margueron, R. & Reinberg, D. The Polycomb complex PRC2 and its mark in life. Nature 469, 343–349 (2011).
Beroukhim, R. et al. The landscape of somatic copy-number alteration across human cancers. Nature 463, 899–905 (2010).
Hollstein, M., Sidransky, D., Vogelstein, B. & Harris, C.C. p53 mutations in human cancers. Science 253, 49–53 (1991).
Lohmann, D. Retinoblastoma. Adv. Exp. Med. Biol. 685, 220–227 (2010).
Stephens, P.J. et al. Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell 144, 27–40 (2011).
Rausch, T. et al. Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations. Cell 148, 59–71 (2012).
Hanel, W. & Moll, U.M. Links between mutant p53 and genomic instability. J. Cell. Biochem. 113, 433–439 (2012).
Li, M. et al. The ATM-p53 pathway suppresses aneuploidy-induced tumorigenesis. Proc. Natl. Acad. Sci. USA 107, 14188–14193 (2010).
Thompson, S.L. & Compton, D.A. Proliferation of aneuploid human cells is limited by a p53-dependent mechanism. J. Cell Biol. 188, 369–381 (2010).
Deshpande, A. & Hinds, P.W. The retinoblastoma protein in osteoblast differentiation and osteosarcoma. Curr. Mol. Med. 6, 809–817 (2006).
Romero, F., Martinez, A.C., Camonis, J. & Rebollo, A. Aiolos transcription factor controls cell death in T cells by regulating Bcl-2 expression and its cellular localization. EMBO J. 18, 3419–3430 (1999).
Krzywinski, M. et al. Circos: an information aesthetic for comparative genomics. Genome Res. 19, 1639–1645 (2009).
Boulos, N. et al. Chemotherapeutic agents circumvent emergence of dasatinib-resistant BCR-ABL kinase mutations in a precise mouse model of Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood 117, 3585–3595 (2011).
Ding, L. et al. Genome remodelling in a basal-like breast cancer metastasis and xenograft. Nature 464, 999–1005 (2010).
Mardis, E.R. et al. Recurring mutations found by sequencing an acute myeloid leukemia genome. N. Engl. J. Med. 361, 1058–1066 (2009).
Downing, J.R. et al. The Pediatric Cancer Genome Project. Nat. Genet. 44, 619–622 (2012).
Sherry, S.T. et al. dbSNP: the NCBI database of genetic variation. Nucleic Acids Res. 29, 308–311 (2001).
Lin, M. et al. dChipSNP: significance curve and clustering of SNP-array-based loss-of-heterozygosity data. Bioinformatics 20, 1233–1240 (2004).
Venkatraman, E.S. & Olshen, A.B. A faster circular binary segmentation algorithm for the analysis of array CGH data. Bioinformatics 23, 657–663 (2007).
Rozen, S. & Skaletsky, H.J. Bioinformatics Methods and Protocols (Methods in Molecular Biology). (Humana Press, 2000).
Zhang, J. et al. SNPdetector: a software tool for sensitive and accurate SNP detection. PLOS Comput. Biol. 1, e53 (2005).
Chen, K. et al. PolyScan: an automatic indel and SNP detection approach to the analysis of human resequencing data. Genome Res. 17, 659–666 (2007).
Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. USA 102, 15545–15550 (2005).
Donovan, S., See, W., Bonifas, J., Stokoe, D. & Shannon, K.M. Hyperactivation of protein kinase B and ERK have discrete effects on survival, proliferation, and cytokine expression in Nf1-deficient myeloid cells. Cancer Cell 2, 507–514 (2002).
Schubbert, S. et al. Germline KRAS mutations cause Noonan syndrome. Nat. Genet. 38, 331–336 (2006).
Peto, R. et al. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. analysis and examples. Br. J. Cancer 35, 1–39 (1977).
Mantel, N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother. Rep. 50, 163–170 (1966).
Fine, J.P. & Gray, R.J. A proportional hazards model for the subdistribution of a competing risk. J. Am. Stat. Assoc. 94, 496–509 (1999).
R Development Core Team. R: a language and environment for statistical computing (R Foundation for Statistical Computing, Vienna, 2006).