The Epigenetic Landscape of Aneuploidy: Constitutional Mosaicism Leading the Way?

References

• Hassold T , HuntP . To err (meiotically) is human: the genesis of human aneuploidy . Nat. Rev. Genet.2 ( 4 ), 280 – 291 ( 2001 ).
   PubMed Web of Science ®Google Scholar
• Abruzzo MA , MayerM , JacobsPA . Aging and aneuploidy: evidence for the preferential involvement of the inactive X chromosome . Cytogenetics Cell Genet.39 ( 4 ), 275 – 278 ( 1985 ).
   PubMedGoogle Scholar
• Surralles J , JeppesenP , MorrisonH , NatarajanAT . Analysis of loss of inactive X chromosomes in interphase cells . Am. J. Hum. Genet.59 ( 5 ), 1091 – 1096 ( 1996 ).
   PubMed Web of Science ®Google Scholar
• Catalan J , FalckGC , NorppaH . The X chromosome frequently lags behind in female lymphocyte anaphase . Am. J. Hum. Genet.66 ( 2 ), 687 – 691 ( 2000 ).
   PubMed Web of Science ®Google Scholar
• Hsu LY , KaffeS , JenkinsECet al. Proposed guidelines for diagnosis of chromosome mosaicism in amniocytes based on data derived from chromosome mosaicism and pseudomosaicism studies . Prenat. Diagn.12 ( 7 ), 555 – 573 ( 1992 ).
   PubMed Web of Science ®Google Scholar
• Hsu LY , YuMT , RichkindKEet al. Incidence and significance of chromosome mosaicism involving an autosomal structural abnormality diagnosed prenatally through amniocentesis: a collaborative study . Prenat. Diagn.16 ( 1 ), 1 – 28 ( 1996 ).
   PubMed Web of Science ®Google Scholar
• Jacobs KB , YeagerM , ZhouWet al. Detectable clonal mosaicism and its relationship to aging and cancer . Nat. Genet.44 ( 6 ), 651 – 658 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Laurie CC , LaurieCA , RiceKet al. Detectable clonal mosaicism from birth to old age and its relationship to cancer . Nat. Genet.44 ( 6 ), 642 – 650 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Rodriguez-Santiago B , MalatsN , RothmanNet al. Mosaic uniparental disomies and aneuploidies as large structural variants of the human genome . Am. J. Hum. Genet.87 ( 1 ), 129 – 138 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Hanahan D , WeinbergRA . The hallmarks of cancer . Cell100 ( 1 ), 57 – 70 ( 2000 ).
   PubMed Web of Science ®Google Scholar
• Ricke RM , van ReeJH , van DeursenJM . Whole chromosome instability and cancer: a complex relationship . Trends Genet.24 ( 9 ), 457 – 466 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Beroukhim R , MermelCH , PorterDet al. The landscape of somatic copy-number alteration across human cancers . Nature463 ( 7283 ), 899 – 905 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Gordon DJ , ResioB , PellmanD . Causes and consequences of aneuploidy in cancer . Nat. Rev. Genet.13 ( 3 ), 189 – 203 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• NCI. Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer. http://cgap.nci.nih.gov/Chromosomes/Mitelman
   Google Scholar
• Holland AJ , ClevelandDW . Boveri revisited: chromosomal instability, aneuploidy and tumorigenesis . Nat. Rev. Mol. Cell Biol.10 ( 7 ), 478 – 487 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Weaver BAA , SilkAD , MontagnaC , Verdier-PinardP , ClevelandDW . Aneuploidy acts both oncogenically and as a tumor suppressor . Cancer Cell11 ( 1 ), 25 – 36 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Williams BR , PrabhuVR , HunterKEet al. Aneuploidy affects proliferation and spontaneous immortalization in mammalian cells . Science322 ( 5902 ), 703 – 709 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Ganmore I , SmoohaG , IzraeliS . Constitutional aneuploidy and cancer predisposition . Hum. Mol. Genet.18 ( R1 ), R84 – 93 ( 2009 ).
   PubMedGoogle Scholar
• Orphanet. The portal for rare diseases and orphan drugs. www.orpha.net/consor/cgi-bin/index.php
   Google Scholar
• Wiseman FK , AlfordKA , TybulewiczVL , FisherEM . Down syndrome–recent progress and future prospects . Hum. Mol. Genet.18 ( R1 ), R75 – 83 ( 2009 ).
   PubMedGoogle Scholar
• Parker SE , MaiCT , CanfieldMAet al. Updated National Birth Prevalence estimates for selected birth defects in the United States, 2004-2006 . Birth. Defects Res. A. Clin. Mol. Teratol.88 ( 12 ), 1008 – 1016 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Mao R , WangX , SpitznagelJrELet al. Primary and secondary transcriptional effects in the developing human Down syndrome brain and heart . Genome Biol.6 ( 13 ), R107 ( 2005 ).
   PubMed Web of Science ®Google Scholar
• Li CM , GuoM , SalasMet al. Cell type-specific over-expression of chromosome 21 genes in fibroblasts and fetal hearts with trisomy 21 . BMC Med. Genet.7 , 24 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Prandini P , DeutschS , LyleRet al. Natural gene-expression variation in Down syndrome modulates the outcome of gene-dosage imbalance . Am. J. Hum. Genet.81 ( 2 ), 252 – 263 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Rozovski U , Jonish-GrossmanA , Bar-ShiraA , OchshornY , GoldsteinM , YaronY . Genome-wide expression analysis of cultured trophoblast with trisomy 21 karyotype . Hum. Reprod.22 ( 9 ), 2538 – 2545 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Kerkel K , SchupfN , HattaKet al. Altered DNA methylation in leukocytes with trisomy 21 . PLOS Genet.6 ( 11 ), e1001212 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Jin S , LeeYK , LimYCet al. Global DNA hypermethylation in down syndrome placenta . PLOS Genet.9 ( 6 ), e1003515 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Jiang J , JingY , CostGJet al. Translating dosage compensation to trisomy 21 . Nature500 ( 7462 ), 296 – 300 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• FitzPatrick DR , RamsayJ , McGillNI , ShadeM , CarothersAD , HastieND . Transcriptome analysis of human autosomal trisomy . Hum. Mol. Genet.11 ( 26 ), 3249 – 3256 ( 2002 ).
   PubMed Web of Science ®Google Scholar
• Altug-Teber Ö , BoninM , WalterMet al. Specific transcriptional changes in human fetuses with autosomal trisomies . Cytogenet. Genome Res.119 ( 3-4 ), 171 – 184 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Biancotti JC , NarwaniK , BuehlerNet al. Human embryonic stem cells as models for aneuploid chromosomal syndromes . Stem Cells28 ( 9 ), 1530 – 1540 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Davidsson J , VeerlaS , JohanssonB . Constitutional trisomy 8 mosaicism as a model for epigenetic studies of aneuploidy . Epigenetics Chromatin6 ( 1 ), 18 ( 2013 ).
   PubMedGoogle Scholar
• Gorlin RJ , CohenMM , HennekamRCM . Syndromes of the Head and Neck . Oxford University Press , Oxford, UK ( 2001 ).
   Google Scholar
• Hale NE , KeaneJFJr . Piecing together a picture of trisomy 8 mosaicism syndrome . J. Am. Osteopath. Assoc.110 ( 1 ), 21 – 23 ( 2010 ).
   PubMedGoogle Scholar
• Riccardi VM . Trisomy 8: an international study of 70 patients . Birth Defects Orig. Artic. Ser.13 ( 3C ), 171 – 184 ( 1977 ).
   PubMedGoogle Scholar
• DeBrasi D , GenardiM , D’AgostinoAet al. Double autosomal/gonosomal mosaic aneuploidy: study of nondisjunction in two cases with trisomy of chromosome 8 . Hum. Genet.95 ( 5 ), 519 – 525 ( 1995 ).
   PubMed Web of Science ®Google Scholar
• Robinson WP , BinkertF , BernasconiF , Lorda-SanchezI , WerderEA , SchinzelAA . Molecular studies of chromosomal mosaicism: relative frequency of chromosome gain or loss and possible role of cell selection . Am. J. Hum. Genet.56 ( 2 ), 444 – 451 ( 1995 ).
   PubMed Web of Science ®Google Scholar
• James RS , JacobsPA . Molecular studies of the aetiology of trisomy 8 in spontaneous abortions and the liveborn population . Hum. Genet.97 ( 3 ), 283 – 286 ( 1996 ).
   PubMed Web of Science ®Google Scholar
• Seghezzi L , MaseratiE , MinelliAet al. Constitutional trisomy 8 as first mutation in multistep carcinogenesis: clinical, cytogenetic, and molecular data on three cases . Genes Chromosomes Cancer17 ( 2 ), 94 – 101 ( 1996 ).
   PubMed Web of Science ®Google Scholar
• Karadima G , BuggeM , NicolaidisPet al. Origin of nondisjunction in trisomy 8 and trisomy 8 mosaicism . Eur. J. Hum. Genet.6 ( 5 ), 432 – 438 ( 1998 ).
   PubMed Web of Science ®Google Scholar
• Lamb NE , FreemanSB , Savage-AustinAet al. Susceptible chiasmate configurations of chromosome 21 predispose to non-disjunction in both maternal meiosis I and meiosis II . Nat. Genet.14 ( 4 ), 400 – 405 ( 1996 ).
   PubMed Web of Science ®Google Scholar
• Veitia RA , BottaniS , BirchlerJA . Cellular reactions to gene dosage imbalance: genomic, transcriptomic and proteomic effects . Trends Genet.24 ( 8 ), 390 – 397 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Virtaneva K , WrightFA , TannerSMet al. Expression profiling reveals fundamental biological differences in acute myeloid leukemia with isolated trisomy 8 and normal cytogenetics . Proc. Natl. Acad. Sci. USA98 ( 3 ), 1124 – 1129 ( 2001 ).
   PubMed Web of Science ®Google Scholar
• Vey N , MozziconacciMJ , Groulet-MartinecAet al. Identification of new classes among acute myelogenous leukaemias with normal karyotype using gene expression profiling . Oncogene23 ( 58 ), 9381 – 9391 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Schoch C , KohlmannA , DugasM , KernW , SchnittgerS , HaferlachT . Impact of trisomy 8 on expression of genes located on chromosome 8 in different AML subgroups . Genes Chromosomes Cancer45 ( 12 ), 1164 – 1168 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Riccardi VM . Trisomy 8 mosaicism in the skin of a patient with leukemia . Birth Defects Orig. Artic. Ser.12 ( 1 ), 187 ( 1976 ).
   PubMedGoogle Scholar
• Gafter U , ShabtalF , KahnY , HalbrechtI , DjaldettiM . Aplastic anemia followed by leukemia in congenital trisomy 8 mosaicism. Ultrastructural studies of polymorphonuclear cells in peripheral blood . Clin. Genet.9 ( 2 ), 134 – 142 ( 1976 ).
   PubMed Web of Science ®Google Scholar
• Riccardi VM , HumbertJR , PeakmanD . Acute leukemia associated with trisomy 8 mosaicism and a familial translocation 46,XY,t(7;20)(p13;p12) . Am. J. Med. Genet.2 ( 1 ), 15 – 21 ( 1978 ).
   PubMed Web of Science ®Google Scholar
• Cornaglia-Ferraris P , GhioR , BarabinoAet al. [Diminished in vitro colony forming capacity of bone marrow cells in a case of chromosome 8 trisomy (mosaicism): criteria for “high risk” pre-leukemia syndrome] . Boll. Ist. Sieroter. Milan60 ( 1 ), 69 – 73 ( 1981 ).
   PubMedGoogle Scholar
• Palmer CG , ProvisorAJ , WeaverDD , HodesME , HeeremaN . Juvenile chronic granulocytic leukemia in a patient with trisomy 8, neurofibromatosis, and prolonged Epstein-Barr virus infection . J. Pediatr.102 ( 6 ), 888 – 892 ( 1983 ).
   PubMed Web of Science ®Google Scholar
• Kapaun P , KabischH , HeldKR , WalterTA , HegewischS , ZanderAR . Atypical chronic myelogenous leukemia in a patient with trisomy 8 mosaicism syndrome . Ann. Hematol.66 ( 1 ), 57 – 58 ( 1993 ).
   PubMed Web of Science ®Google Scholar
• Hasle H , ClausenN , PedersenB , Bendix-HansenK . Myelodysplastic syndrome in a child with constitutional trisomy 8 mosaicism and normal phenotype . Cancer Genet. Cytogenet.79 ( 1 ), 79 – 81 ( 1995 ).
   PubMedGoogle Scholar
• Mastrangelo R , TorneselloA , MastrangeloS , ZollinoM , NeriG . Constitutional trisomy 8 mosaicism evolving to primary myelodysplastic syndrome: a new subset of biologically related patients?Am. J. Hematol.48 ( 1 ), 67 – 68 ( 1995 ).
   PubMed Web of Science ®Google Scholar
• Zollino M , GenuardiM , BajerJet al. Constitutional trisomy 8 and myelodysplasia: report of a case and review of the literature . Leuk. Res.19 ( 10 ), 733 – 736 ( 1995 ).
   PubMed Web of Science ®Google Scholar
• Brady AF , WatersCS , PochaMJ , BruetonLA . Chronic myelomonocytic leukaemia in a child with constitutional partial trisomy 8 mosaicism . Clin. Genet.58 ( 2 ), 142 – 146 ( 2000 ).
   PubMed Web of Science ®Google Scholar
• Narendran A , HawkinsLM , GanjaviHet al. Characterization of bone marrow stromal abnormalities in a patient with constitutional trisomy 8 mosaicism and myelodysplastic syndrome . Pediatr. Hematol. Oncol.21 ( 3 ), 209 – 221 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Welborn J . Constitutional chromosome aberrations as pathogenetic events in hematologic malignancies . Cancer Genet. Cytogenet.149 ( 2 ), 137 – 153 ( 2004 ).
   PubMedGoogle Scholar
• Ando S , MaemoriM , SakaiH , ShiraishiH , SakaiK , RuhnkeGW . Constitutional trisomy 8 mosaicism with myelodysplastic syndrome complicated by intestinal Behcet disease and antithrombin III deficiency . Cancer Genet. Cytogenet.162 ( 2 ), 172 – 175 ( 2005 ).
   PubMedGoogle Scholar
• Maserati E , PressatoB , ValliRet al. Constitutional trisomy 8 mosaicism in primary myelofibrosis: relevance to clinical practice and warning for trisomy 8 studies . Cancer Genet. Cytogenet.179 ( 1 ), 79 – 81 ( 2007 ).
   PubMedGoogle Scholar
• Yamamoto K , OkamuraA , KawanoH , KatayamaY , ShimoyamaM , MatsuiT . A novel t(8;18)(q13;q21) in acute monocytic leukemia evolving from constitutional trisomy 8 mosaicism . Cancer Genet. Cytogenet.176 ( 2 ), 144 – 149 ( 2007 ).
   PubMedGoogle Scholar
• Maserati E , ApriliF , VinanteFet al. Trisomy 8 in myelodysplasia and acute leukemia is constitutional in 15-20% of cases . Genes Chromosomes Cancer33 ( 1 ), 93 – 97 ( 2002 ).
   PubMed Web of Science ®Google Scholar
• Paulsson K , JohanssonB . Trisomy 8 as the sole chromosomal aberration in acute myeloid leukemia and myelodysplastic syndromes . Pathol. Biol. (Paris)55 ( 1 ), 37 – 48 ( 2007 ).
   PubMedGoogle Scholar
• Riggs AD . X inactivation, differentiation, and DNA methylation . Cytogenet. Cell Genet.14 ( 1 ), 9 – 25 ( 1975 ).
   PubMedGoogle Scholar
• Holliday R , PughJE . DNA modification mechanisms and gene activity during development . Science187 ( 4173 ), 226 – 232 ( 1975 ).
   PubMed Web of Science ®Google Scholar
• Bird AP . CpG-rich islands and the function of DNA methylation . Nature321 ( 6067 ), 209 – 213 ( 1986 ).
   PubMed Web of Science ®Google Scholar
• Gardiner-Garden M , FrommerM . CpG islands in vertebrate genomes . J. Mol. Biol.196 ( 2 ), 261 – 282 ( 1987 ).
   PubMed Web of Science ®Google Scholar
• Bird A , TaggartM , FrommerM , MillerOJ , MacleodD . A fraction of the mouse genome that is derived from islands of nonmethylated, CpG-rich DNA . Cell40 ( 1 ), 91 – 99 ( 1985 ).
   PubMed Web of Science ®Google Scholar
• Boyes J , BirdA . Repression of genes by DNA methylation depends on CpG density and promoter strength: evidence for involvement of a methyl-CpG binding protein . EMBO J.11 ( 1 ), 327 – 333 ( 1992 ).
   PubMed Web of Science ®Google Scholar
• Hsieh CL . Dependence of transcriptional repression on CpG methylation density . Mol. Cell Biol.14 ( 8 ), 5487 – 5494 ( 1994 ).
   PubMed Web of Science ®Google Scholar
• Nan X , NgHH , JohnsonCAet al. Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex . Nature393 ( 6683 ), 386 – 389 ( 1998 ).
   PubMed Web of Science ®Google Scholar
• Jones PA . The DNA methylation paradox . Trends Genet.15 ( 1 ), 34 – 37 ( 1999 ).
   PubMed Web of Science ®Google Scholar
• Irizarry RA , Ladd-AcostaC , WenBet al. The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores . Nat. Genet.41 ( 2 ), 178 – 186 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Davidsson J , LilljebjornH , AnderssonAet al. The DNA methylome of pediatric acute lymphoblastic leukemia . Hum. Mol. Genet.18 ( 21 ), 4054 – 4065 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Weber M , DaviesJJ , WittigDet al. Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells . Nat. Genet.37 ( 8 ), 853 – 862 ( 2005 ).
   PubMed Web of Science ®Google Scholar
• Hershey AD , DixonJ , ChaseM . Nucleic acid economy in bacteria infected with bacteriophage T2. I. Purine and pyrimidine composition . J. Gen. Physiol.36 ( 6 ), 777 – 789 ( 1953 ).
   PubMed Web of Science ®Google Scholar
• Penn NW , SuwalskiR , O’RileyC , BojanowskiK , YuraR . The presence of 5-hydroxymethylcytosine in animal deoxyribonucleic acid . Biochem. J.126 ( 4 ), 781 – 790 ( 1972 ).
   PubMed Web of Science ®Google Scholar
• Kriaucionis S , HeintzN . The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain . Science324 ( 5929 ), 929 – 930 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Tahiliani M , KohKP , ShenYet al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1 . Science324 ( 5929 ), 930 – 935 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Ito S , D’AlessioAC , TaranovaOV , HongK , SowersLC , ZhangY . Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification . Nature466 ( 7310 ), 1129 – 1133 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Xu W , YangH , LiuYet al. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases . Cancer Cell19 ( 1 ), 17 – 30 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Valinluck V , SowersLC . Endogenous cytosine damage products alter the site selectivity of human DNA maintenance methyltransferase DNMT1 . Cancer Res.67 ( 3 ), 946 – 950 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Valinluck V , TsaiHH , RogstadDK , BurdzyA , BirdA , SowersLC . Oxidative damage to methyl-CpG sequences inhibits the binding of the methyl-CpG binding domain (MBD) of methyl-CpG binding protein 2 (MeCP2) . Nucleic Acids Res.32 ( 14 ), 4100 – 4108 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Mellen M , AyataP , DewellS , KriaucionisS , HeintzN . MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system . Cell151 ( 7 ), 1417 – 1430 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Nestor CE , OttavianoR , ReddingtonJet al. Tissue type is a major modifier of the 5-hydroxymethylcytosine content of human genes . Genome Res.22 ( 3 ), 467 – 477 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Pfeifer GP , KadamS , JinSG . 5-hydroxymethylcytosine and its potential roles in development and cancer . Epigenetics Chromatin6 ( 1 ), 10 ( 2013 ).
   PubMedGoogle Scholar
• Stroud H , FengS , MoreyKinney S , PradhanS , JacobsenSE . 5-hydroxymethylcytosine is associated with enhancers and gene bodies in human embryonic stem cells . Genome Biol.12 ( 6 ), R54 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Ficz G , BrancoMR , SeisenbergerSet al. Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation . Nature473 ( 7347 ), 398 – 402 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Pastor WA , PapeUJ , HuangYet al. Genome-wide mapping of 5-hydroxymethylcytosine in embryonic stem cells . Nature473 ( 7347 ), 394 – 397 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Jin SG , Jiang Y , Qiu R et al. 5-Hydroxymethylcytosine is strongly depleted in human cancers but its levels do not correlate with IDH1 mutations . Cancer Res.71 ( 24 ), 7360 – 7365 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Lian CG , XuY , CeolCet al. Loss of 5-hydroxymethylcytosine is an epigenetic hallmark of melanoma . Cell150 ( 6 ), 1135 – 1146 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Shih AH , Abdel-WahabO , PatelJP , LevineRL . The role of mutations in epigenetic regulators in myeloid malignancies . Nat. Rev. Cancer12 ( 9 ), 599 – 612 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Hellman A , ChessA . Gene body-specific methylation on the active X chromosome . Science315 ( 5815 ), 1141 – 1143 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Yasukochi Y , MaruyamaO , MahajanMCet al. X chromosome-wide analyses of genomic DNA methylation states and gene expression in male and female neutrophils . Proc. Natl. Acad. Sci. USA107 ( 8 ), 3704 – 3709 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Sharp AJ , StathakiE , MigliavaccaEet al. DNA methylation profiles of human active and inactive X chromosomes . Genome Res.21 ( 10 ), 1592 – 1600 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Szulwach KE , LiX , LiYet al. 5-hmC-mediated epigenetic dynamics during postnatal neurodevelopment and aging . Nat. Neurosci.14 ( 12 ), 1607 – 1616 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Surani MA , BartonSC , NorrisML . Development of reconstituted mouse eggs suggests imprinting of the genome during gametogenesis . Nature308 ( 5959 ), 548 – 550 ( 1984 ).
   PubMed Web of Science ®Google Scholar
• McGrath J , SolterD . Completion of mouse embryogenesis requires both the maternal and paternal genomes . Cell37 ( 1 ), 179 – 183 ( 1984 ).
   PubMed Web of Science ®Google Scholar
• Engel E. A new genetic conceptuniparental disomy and its potential effect, isodisomy . Am. J. Med. Genet.6 ( 2 ), 137 – 143 ( 1980 ).
   PubMed Web of Science ®Google Scholar
• Lim DH , MaherER . Human imprinting syndromes . Epigenomics1 ( 2 ), 347 – 369 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Haas OA . Is genomic imprinting involved in the pathogenesis of hyperdiploid and haploid acute lymphoblastic leukemia of childhood?Acta. Genet. Med. Gemellol. (Roma)45 ( 1-2 ), 239 – 242 ( 1996 ).
   PubMedGoogle Scholar
• Paulsson K , PanagopoulosI , KnuutilaSet al. Formation of trisomies and their parental origin in hyperdiploid childhood acute lymphoblastic leukemia . Blood102 ( 8 ), 3010 – 3015 ( 2003 ).
   PubMed Web of Science ®Google Scholar
• Wilson JL , MorisonIM . No evidence for preferential maternal origin of duplicated chromosome 14 in hyperdiploid ALL . Blood105 ( 4 ), 1837; author reply 1838 ( 2005 ).
   Web of Science ®Google Scholar
• Heyman M , GranderD , Brondum-NielsenK , LiuY , SoderhallS , EinhornS . Deletions of the short arm of chromosome 9, including the interferon-alpha/-beta genes, in acute lymphocytic leukemia. Studies on loss of heterozygosity, parental origin of deleted genes and prognosis . Int. J. Cancer54 ( 5 ), 748 – 753 ( 1993 ).
   PubMed Web of Science ®Google Scholar
• Morison IM , EllisLM , TeagueLR , ReeveAE . Preferential loss of maternal 9p alleles in childhood acute lymphoblastic leukemia . Blood99 ( 1 ), 375 – 377 ( 2002 ).
   PubMed Web of Science ®Google Scholar
• Mullighan CG , PhillipsLA , SuXet al. Genomic analysis of the clonal origins of relapsed acute lymphoblastic leukemia . Science322 ( 5906 ), 1377 – 1380 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Timp W , FeinbergAP . Cancer as a dysregulated epigenome allowing cellular growth advantage at the expense of the host . Nat. Rev. Cancer13 ( 7 ), 497 – 510 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Torres EM , SokolskyT , TuckerCMet al. Effects of aneuploidy on cellular physiology and cell division in haploid yeast . Science317 ( 5840 ), 916 – 924 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Gasch AP , SpellmanPT , KaoCMet al. Genomic expression programs in the response of yeast cells to environmental changes . Mol. Biol. Cell11 ( 12 ), 4241 – 4257 ( 2000 ).
   PubMed Web of Science ®Google Scholar
• Pavelka N , RancatiG , ZhuJet al. Aneuploidy confers quantitative proteome changes and phenotypic variation in budding yeast . Nature468 ( 7321 ), 321 – 325 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Gondor A , OhlssonR . Chromosome crosstalk in three dimensions . Nature461 ( 7261 ), 212 – 217 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Cremer T , CremerM . Chromosome territories . Cold Spring Harbor Persp. Biol.2 ( 3 ), a003889 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Gilbert N , ThomsonI , BoyleS , AllanJ , RamsahoyeB , BickmoreWA . DNA methylation affects nuclear organization, histone modifications, and linker histone binding but not chromatin compaction . J. Cell Biol.177 ( 3 ), 401 – 411 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Hansen KD , TimpW , BravoHCet al. Increased methylation variation in epigenetic domains across cancer types . Nat. Genet.43 ( 8 ), 768 – 775 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Berman BP , WeisenbergerDJ , AmanJFet al. Regions of focal DNA hypermethylation and long-range hypomethylation in colorectal cancer coincide with nuclear lamina-associated domains . Nat. Genet.44 ( 1 ), 40 – 46 ( 2012 ).
   Web of Science ®Google Scholar
• Wen B , WuH , ShinkaiY , IrizarryRA , FeinbergAP . Large histone H3 lysine 9 dimethylated chromatin blocks distinguish differentiated from embryonic stem cells . Nat. Genet.41 ( 2 ), 246 – 250 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Reddy KL , ZulloJM , BertolinoE , SinghH . Transcriptional repression mediated by repositioning of genes to the nuclear lamina . Nature452 ( 7184 ), 243 – 247 ( 2008 ).
   PubMed Web of Science ®Google Scholar