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Abstract

Developments over the past five years have significantly advanced our ability to use genome-scale analyses—including high-density genotyping, transcriptome sequencing, exome sequencing, and genome sequencing—to identify the genetic basis of childhood cancer. This article reviews several key results from an expanding number of genomic studies of pediatric cancer: () Histopathologic subtypes of cancers can be associated with a high incidence of germline predisposition, () neurodevelopmental disorders or highly penetrant cancer predisposition syndromes can result from specific patterns of variation in genes encoding the SMARC family of chromatin remodelers, () genome-wide association studies with relatively small pediatric cancer cohorts have successfully identified single-nucleotide polymorphisms with large effect sizes and provided insight into population differences in cancer risk, and () multiple exome or genome analyses of unselected childhood cancer cohorts have yielded a 7–10% incidence of pathogenic variants in cancer predisposition genes. This work supports the increasing use of genomic sequencing in the care of pediatric cancer patients and at-risk family members.

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2019-08-31
2024-04-23
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Literature Cited

  1. 1.
    Agopian AJ, Eastcott LM, Mitchell LE 2012. Age of onset and effect size in genome-wide association studies. Birth Defects Res. A 94:908–11
    [Google Scholar]
  2. 2.
    Am. Assoc. Cancer Res. 2017. Pediatric Oncology Series. Clinical Cancer Research http://clincancerres.aacrjournals.org/pediatricseries
    [Google Scholar]
  3. 3.
    Amayiri N, Tabori U, Campbell B, Bakry D, Aronson M et al. 2016. High frequency of mismatch repair deficiency among pediatric high grade gliomas in Jordan. Int. J. Cancer 138:380–85
    [Google Scholar]
  4. 4.
    Archer NP, Perez-Andreu V, Scheurer ME, Rabin KR, Peckham-Gregory EC et al. 2016. Family-based exome-wide assessment of maternal genetic effects on susceptibility to childhood B-cell acute lymphoblastic leukemia in Hispanics. Cancer 122:3697–704
    [Google Scholar]
  5. 5.
    Archer NP, Perez-Andreu V, Stoltze U, Scheurer ME, Wilkinson AV et al. 2017. Family-based exome-wide association study of childhood acute lymphoblastic leukemia among Hispanics confirms role of ARID5B in susceptibility. PLOS ONE 12:e0180488
    [Google Scholar]
  6. 6.
    Deleted in proof
  7. 7.
    Bakry D, Aronson M, Durno C, Rimawi H, Farah R et al. 2014. Genetic and clinical determinants of constitutional mismatch repair deficiency syndrome: report from the constitutional mismatch repair deficiency consortium. Eur. J. Cancer 50:987–96
    [Google Scholar]
  8. 8.
    Biegel JA, Zhou JY, Rorke LB, Stenstrom C, Wainwright LM, Fogelgren B 1999. Germ-line and acquired mutations of INI1 in atypical teratoid and rhabdoid tumors. Cancer Res 59:74–79
    [Google Scholar]
  9. 9.
    Bien SA, Wojcik GL, Zubair N, Gignoux CR, Martin AR et al. 2016. Strategies for enriching variant coverage in candidate disease loci on a multiethnic genotyping array. PLOS ONE 11:e0167758
    [Google Scholar]
  10. 10.
    Bogershausen N, Wollnik B. 2018. Mutational landscapes and phenotypic spectrum of SWI/SNF-related intellectual disability disorders. Front. Mol. Neurosci. 11:252
    [Google Scholar]
  11. 11.
    Brodeur GM, Nichols KE, Plon SE, Schiffman JD, Malkin D 2017. Pediatric cancer predisposition and surveillance: an overview, and a tribute to Alfred G. Knudson Jr. Clin. Cancer Res. 23:e1–5
    [Google Scholar]
  12. 12.
    Brohl AS, Patidar R, Turner CE, Wen X, Song YK et al. 2017. Frequent inactivating germline mutations in DNA repair genes in patients with Ewing sarcoma. Genet. Med. 19:955–58
    [Google Scholar]
  13. 13.
    Bruggers CS, Bleyl SB, Pysher T, Barnette P, Afify Z et al. 2011. Clinicopathologic comparison of familial versus sporadic atypical teratoid/rhabdoid tumors (AT/RT) of the central nervous system. Pediatr. Blood Cancer 56:1026–31
    [Google Scholar]
  14. 14.
    Churchman ML, Qian M, te Kronnie G, Zhang R, Yang W et al. 2018. Germline genetic IKZF1 variation and predisposition to childhood acute lymphoblastic leukemia. Cancer Cell 33:937–48.e8
    [Google Scholar]
  15. 15.
    Deleted in proof
  16. 16.
    Diets IJ, Prescott T, Champaigne NL, Mancini GMS, Krossnes B et al. 2019. A recurrent de novo missense pathogenic variant in SMARCB1 causes severe intellectual disability and choroid plexus hyperplasia with resultant hydrocephalus. Genet. Med. 21:572–79
    [Google Scholar]
  17. 17.
    Eaton K, Tooke LS, Wainwright LM, Judkins AR, Biegel JA 2010. Spectrum of SMARCB1/INI1 mutations in familial and sporadic rhabdoid tumors. Pediatr. Blood Cancer 56:7–15
    [Google Scholar]
  18. 18.
    Eleveld TF, Oldridge DA, Bernard V, Koster J, Daage LC et al. 2015. Relapsed neuroblastomas show frequent RAS-MAPK pathway mutations. Nat. Genet. 47:864–71
    [Google Scholar]
  19. 19.
    Ellinghaus E, Stanulla M, Richter G, Ellinghaus D, te Kronnie G et al. 2012. Identification of germline susceptibility loci in ETV6-RUNX1-rearranged childhood acute lymphoblastic leukemia. Leukemia 26:902–9
    [Google Scholar]
  20. 20.
    Felix CA, D'Amico D, Mitsudomi T, Nau MM, Li FP et al. 1992. Absence of hereditary p53 mutations in 10 familial leukemia pedigrees. J. Clin. Investig. 90:653–58
    [Google Scholar]
  21. 21.
    Feurstein S, Drazer MW, Godley LA 2016. Genetic predisposition to leukemia and other hematologic malignancies. Semin. Oncol. 43:598–608
    [Google Scholar]
  22. 22.
    Foulkes WD, Clarke BA, Hasselblatt M, Majewski J, Albrecht S, McCluggage WG 2014. No small surprise – small cell carcinoma of the ovary, hypercalcaemic type, is a malignant rhabdoid tumour. J. Pathol. 233:209–14
    [Google Scholar]
  23. 23.
    Fraumeni JF, Glass AG. 1970. Rarity of Ewing's sarcoma among U.S. Negro children. Lancet 295:366–67
    [Google Scholar]
  24. 24.
    George RE, Attiyeh EF, Li S, Moreau LA, Neuberg D et al. 2007. Genome-wide analysis of neuroblastomas using high-density single nucleotide polymorphism arrays. PLOS ONE 2:e255
    [Google Scholar]
  25. 25.
    Gossai N, Biegel JA, Messiaen L, Berry SA, Moertel CL 2015. Report of a patient with a constitutional missense mutation in SMARCB1, Coffin-Siris phenotype, and schwannomatosis. Am. J. Med. Genet. A 167A:3186–91
    [Google Scholar]
  26. 26.
    Goudie C, Coltin H, Witkowski L, Mourad S, Malkin D, Foulkes WD 2017. The McGill Interactive Pediatric OncoGenetic Guidelines: an approach to identifying pediatric oncology patients most likely to benefit from a genetic evaluation. Pediatr. Blood Cancer 64:e26441
    [Google Scholar]
  27. 27.
    Gröbner SN, Worst BC, Weischenfeldt J, Buchhalter I, Kleinheinz K et al. 2018. The landscape of genomic alterations across childhood cancers. Nature 555:321–27
    [Google Scholar]
  28. 28.
    Grossbach AJ, Mahaney KB, Menezes AH 2017. Pediatric meningiomas: 65-year experience at a single institution. J. Neurosurg. Pediatr. 20:42–50
    [Google Scholar]
  29. 29.
    Grünewald TGP, Bernard V, Gilardi-Hebenstreit P, Raynal V, Surdez D et al. 2015. Chimeric EWSR1-FLI1 regulates the Ewing sarcoma susceptibility gene EGR2 via a GGAA microsatellite. Nat. Genet. 47:1073–78
    [Google Scholar]
  30. 30.
    Holmfeldt L, Wei L, Diaz-Flores E, Walsh M, Zhang J et al. 2013. The genomic landscape of hypodiploid acute lymphoblastic leukemia. Nat. Genet. 45:242–52
    [Google Scholar]
  31. 30a.
    Huang KL, Mashl RJ, Wu Y, Ritter DI, Wang J et al. 2018. Pathogenic germline variants in 10,389 adult cancers. Cell 173:355–70.e14
    [Google Scholar]
  32. 31.
    Hulsebos TJ, Plomp AS, Wolterman RA, Robanus-Maandag EC, Baas F, Wesseling P 2007. Germline mutation of INI1/SMARCB1 in familial schwannomatosis. Am. J. Hum. Genet. 80:805–10
    [Google Scholar]
  33. 32.
    Jawad MU, Cheung MC, Min ES, Schneiderbauer MM, Koniaris LG, Scully SP 2009. Ewing sarcoma demonstrates racial disparities in incidence-related and sex-related differences in outcome: an analysis of 1631 cases from the SEER database, 1973–2005. Cancer 115:3526–36
    [Google Scholar]
  34. 33.
    Kehrer-Sawatzki H, Farschtschi S, Mautner VF, Cooper DN 2017. The molecular pathogenesis of schwannomatosis, a paradigm for the co-involvement of multiple tumour suppressor genes in tumorigenesis. Hum. Genet. 136:129–48
    [Google Scholar]
  35. 34.
    Kosho T, Okamoto N, Ohashi H, Tsurusaki Y, Imai Y et al. 2013. Clinical correlations of mutations affecting six components of the SWI/SNF complex: detailed description of 21 patients and a review of the literature. Am. J. Med. Genet. A 161A:1221–37
    [Google Scholar]
  36. 35.
    Lam C, Ou JC, Billingsley EM 2013. “PTCH”-ing it together: a basal cell nevus syndrome review. Dermatol. Surg. 39:1557–72
    [Google Scholar]
  37. 36.
    Deleted in proof
  38. 37.
    Larouche V, Atkinson J, Albrecht S, Laframboise R, Jabado N et al. 2018. Sustained complete response of recurrent glioblastoma to combined checkpoint inhibition in a young patient with constitutional mismatch repair deficiency. Pediatr. Blood Cancer 65:e27389
    [Google Scholar]
  39. 38.
    Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E et al. 2016. Analysis of protein-coding genetic variation in 60,706 humans. Nature 536:285–91
    [Google Scholar]
  40. 39.
    Li FP, Fraumeni JF Jr, Mulvihill JJ, Blattner WA, Dreyfus MG et al. 1988. A cancer family syndrome in twenty-four kindreds. Cancer Res 48:5358–62
    [Google Scholar]
  41. 40.
    Ma X, Liu Y, Liu Y, Alexandrov LB, Edmonson MN et al. 2018. Pan-cancer genome and transcriptome analyses of 1,699 paediatric leukaemias and solid tumours. Nature 555:371–76
    [Google Scholar]
  42. 41.
    MacArthur J, Bowler E, Cerezo M, Gil L, Hall P et al. 2017. The new NHGRI-EBI Catalog of published genome-wide association studies (GWAS Catalog). Nucleic Acids Res 45:D896–901
    [Google Scholar]
  43. 42.
    Machiela MJ, Grunewald TGP, Surdez D, Reynaud S, Mirabeau O et al. 2018. Genome-wide association study identifies multiple new loci associated with Ewing sarcoma susceptibility. Nat. Commun. 9:3184
    [Google Scholar]
  44. 43.
    Deleted in proof
  45. 44.
    Manolio TA. 2010. Genomewide association studies and assessment of the risk of disease. N. Engl. J. Med. 363:166–76
    [Google Scholar]
  46. 45.
    Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA et al. 2009. Finding the missing heritability of complex diseases. Nature 461:747–53
    [Google Scholar]
  47. 46.
    Maris JM, Mosse YP, Bradfield JP, Hou C, Monni S et al. 2008. Chromosome 6p22 locus associated with clinically aggressive neuroblastoma. N. Engl. J. Med. 358:2585–93
    [Google Scholar]
  48. 47.
    Marks LJ, Oberg JA, Pendrick D, Sireci AN, Glasser C et al. 2017. Precision medicine in children and young adults with hematologic malignancies and blood disorders: the Columbia University experience. Front. Pediatr. 5:265
    [Google Scholar]
  49. 48.
    Mendoza-Londono R, Kashork CD, Shaffer LG, Krance R, Plon SE 2005. Acute lymphoblastic leukemia in a patient with Greig cephalopolysyndactyly and interstitial deletion of chromosome 7 del(7)(p11.2 p14) involving the GLI3 and ZNFN1A1 genes. Genes Chromosomes Cancer 42:82–86
    [Google Scholar]
  50. 49.
    Migliorini G, Fiege B, Hosking FJ, Ma Y, Kumar R et al. 2013. Variation at 10p12.2 and 10p14 influences risk of childhood B-cell acute lymphoblastic leukemia and phenotype. Blood 122:3298–307
    [Google Scholar]
  51. 50.
    Mirabello L, Koster R, Moriarity BS, Spector LG, Meltzer PS et al. 2015. A genome-wide scan identifies variants in NFIB associated with metastasis in patients with osteosarcoma. Cancer Discov 5:920–31
    [Google Scholar]
  52. 51.
    Mirabello L, Richards EG, Duong LM, Yu K, Wang Z et al. 2011. Telomere length and variation in telomere biology genes in individuals with osteosarcoma. Int. J. Mol. Epidemiol. Genet. 2:19–29
    [Google Scholar]
  53. 52.
    Mody RJ, Wu YM, Lonigro RJ, Cao X, Roychowdhury S et al. 2015. Integrative clinical sequencing in the management of refractory or relapsed cancer in youth. JAMA 314:913–25
    [Google Scholar]
  54. 53.
    Moriyama T, Metzger ML, Wu G, Nishii R, Qian M et al. 2015. Germline genetic variation in ETV6 and risk of childhood acute lymphoblastic leukaemia: a systematic genetic study. Lancet Oncol 16:1659–66
    [Google Scholar]
  55. 54.
    Mullighan CG, Goorha S, Radtke I, Miller CB, Coustan-Smith E et al. 2007. Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. Nature 446:758–64
    [Google Scholar]
  56. 55.
    Mullighan CG, Zhang J, Kasper LH, Lerach S, Payne-Turner D et al. 2011. CREBBP mutations in relapsed acute lymphoblastic leukaemia. Nature 471:235–39
    [Google Scholar]
  57. 56.
    Musselman JR, Bergemann TL, Ross JA, Sklar C, Silverstein KA et al. 2012. Case-parent analysis of variation in pubertal hormone genes and pediatric osteosarcoma: a Children's Oncology Group (COG) study. Int. J. Mol. Epidemiol. Genet. 3:286–93
    [Google Scholar]
  58. 57.
    Noetzli L, Lo RW, Lee-Sherick AB, Callaghan M, Noris P et al. 2015. Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia. Nat. Genet. 47:535–38
    [Google Scholar]
  59. 58.
    Oberg JA, Glade Bender JL, Sulis ML, Pendrick D, Sireci AN et al. 2016. Implementation of next generation sequencing into pediatric hematology-oncology practice: moving beyond actionable alterations. Genome Med 8:133
    [Google Scholar]
  60. 59.
    Orsi L, Rudant J, Bonaventure A, Goujon-Bellec S, Corda E et al. 2012. Genetic polymorphisms and childhood acute lymphoblastic leukemia: GWAS of the ESCALE study (SFCE). Leukemia 26:2561–64
    [Google Scholar]
  61. 60.
    Papaemmanuil E, Hosking FJ, Vijayakrishnan J, Price A, Olver B et al. 2009. Loci on 7p12.2, 10q21.2 and 14q11.2 are associated with risk of childhood acute lymphoblastic leukemia. Nat. Genet. 41:1006–10
    [Google Scholar]
  62. 60a.
    Parsons DW, Li M, Zhang X, Jones S, Leary RJ et al. 2011. The genetic landscape of the childhood cancer medulloblastoma. Science 331:435–39
    [Google Scholar]
  63. 61.
    Parsons DW, Roy A, Yang Y, Wang T, Scollon S et al. 2016. Diagnostic yield of clinical tumor and germline whole-exome sequencing for children with solid tumors. JAMA Oncol 2:616–24
    [Google Scholar]
  64. 62.
    Pearson TA, Manolio TA. 2008. How to interpret a genome-wide association study. JAMA 299:1335–44
    [Google Scholar]
  65. 63.
    Peckham-Gregory EC, Chakraborty R, Scheurer ME, Belmont JW, Abhyankar H et al. 2017. A genome-wide association study of LCH identifies a variant in SMAD6 associated with susceptibility. Blood 130:2229–32
    [Google Scholar]
  66. 64.
    Perez-Andreu V, Roberts KG, Harvey RC, Yang W, Cheng C et al. 2013. Inherited GATA3 variants are associated with Ph-like childhood acute lymphoblastic leukemia and risk of relapse. Nat. Genet. 45:1494–98
    [Google Scholar]
  67. 65.
    Piotrowski A, Xie J, Liu YF, Poplawski AB, Gomes AR et al. 2014. Germline loss-of-function mutations in LZTR1 predispose to an inherited disorder of multiple schwannomas. Nat. Genet. 46:182–87
    [Google Scholar]
  68. 66.
    Plon SE, Wheeler DA, Strong LC, Tomlinson GE, Pirics M et al. 2011. Identification of genetic susceptibility to childhood cancer through analysis of genes in parallel. Cancer Genet 204:19–25
    [Google Scholar]
  69. 67.
    Postel-Vinay S, Veron AS, Tirode F, Pierron G, Reynaud S et al. 2012. Common variants near TARDBP and EGR2 are associated with susceptibility to Ewing sarcoma. Nat. Genet. 44:323–27
    [Google Scholar]
  70. 68.
    Postema FAM, Hopman SMJ, Aalfs CM, Berger LPV, Bleeker FE et al. 2017. Childhood tumours with a high probability of being part of a tumour predisposition syndrome; reason for referral for genetic consultation. Eur. J. Cancer 80:48–54
    [Google Scholar]
  71. 69.
    Postema FAM, Hopman SMJ, Hennekam RC, Merks JHM 2018. Consequences of diagnosing a tumor predisposition syndrome in children with cancer: a literature review. Pediatr. Blood Cancer 65:e26718
    [Google Scholar]
  72. 70.
    Powell BC, Jiang L, Muzny DM, Trevino LR, Dreyer ZE et al. 2013. Identification of TP53 as an acute lymphocytic leukemia susceptibility gene through exome sequencing. Pediatr. Blood Cancer 60:E1–3
    [Google Scholar]
  73. 71.
    Qian M, Cao X, Devidas M, Yang W, Cheng C et al. 2018. TP53 germline variations influence the predisposition and prognosis of B-cell acute lymphoblastic leukemia in children. J. Clin. Oncol. 36:591–99
    [Google Scholar]
  74. 72.
    Quinn E, McGee R, Nuccio R, Pappo AS, Nichols KE 2015. Genetic predisposition to neonatal tumors. Curr. Pediatr. Rev. 11:164–78
    [Google Scholar]
  75. 73.
    Rausch T, Jones DT, Zapatka M, Stutz AM, Zichner T et al. 2012. Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations. Cell 148:59–71
    [Google Scholar]
  76. 74.
    Raymond VM, Gray SW, Roychowdhury S, Joffe S, Chinnaiyan AM et al. 2016. Germline findings in tumor-only sequencing: points to consider for clinicians and laboratories. J. Natl. Cancer Inst. 108:djv351
    [Google Scholar]
  77. 75.
    Raynor LA, Pankratz N, Spector LG 2013. An analysis of measures of effect size by age of onset in cancer genomewide association studies. Genes Chromosomes Cancer 52:855–59
    [Google Scholar]
  78. 76.
    Ribeiro KB, Degar B, Antoneli CBG, Rollins B, Rodriguez-Galindo C 2015. Ethnicity, race, and socioeconomic status influence incidence of Langerhans cell histiocytosis. Pediatr. Blood Cancer 62:982–87
    [Google Scholar]
  79. 77.
    Richards S, Aziz N, Bale S, Bick D, Das S et al. 2015. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet. Med. 17:405–24
    [Google Scholar]
  80. 78.
    Ripperger T, Bielack SS, Borkhardt A, Brecht IB, Burkhardt B et al. 2017. Childhood cancer predisposition syndromes—a concise review and recommendations by the Cancer Predisposition Working Group of the Society for Pediatric Oncology and Hematology. Am. J. Med. Genet. A 173:1017–37
    [Google Scholar]
  81. 79.
    Ritenour LE, Randall MP, Bosse KR, Diskin SJ 2018. Genetic susceptibility to neuroblastoma: current knowledge and future directions. Cell Tissue Res 372:287–307
    [Google Scholar]
  82. 80.
    Ruza E, Sotillo E, Sierrasesumaga L, Azcona C, Patino-Garcia A 2003. Analysis of polymorphisms of the vitamin D receptor, estrogen receptor, and collagen Iα1 genes and their relationship with height in children with bone cancer. J. Pediatr. Hematol. Oncol. 25:780–86
    [Google Scholar]
  83. 81.
    Sadetzki S, Bruchim R, Oberman B, Armstrong GN, Lau CC et al. 2013. Description of selected characteristics of familial glioma patients – results from the Gliogene Consortium. Eur. J. Cancer 49:1335–45
    [Google Scholar]
  84. 82.
    Savage SA, Mirabello L, Wang Z, Gastier-Foster JM, Gorlick R et al. 2013. Genome-wide association study identifies two susceptibility loci for osteosarcoma. Nat. Genet. 45:799–803
    [Google Scholar]
  85. 83.
    Savage SA, Modi WS, Douglass CW, Hoover RN, Chanock SJ 2006. Identification of a haplotype block in IGF2R associated with increased risk for osteosarcoma Paper presented at the 97th Annual Meeting of the American Association for Cancer Research Washington, DC: Apr 1–5
    [Google Scholar]
  86. 84.
    Schneppenheim R, Fruhwald MC, Gesk S, Hasselblatt M, Jeibmann A et al. 2010. Germline nonsense mutation and somatic inactivation of SMARCA4/BRG1 in a family with rhabdoid tumor predisposition syndrome. Am. J. Hum. Genet. 86:279–84
    [Google Scholar]
  87. 85.
    Schrader KA, Cheng DT, Joseph V, Prasad M, Walsh M et al. 2016. Germline variants in targeted tumor sequencing using matched normal DNA. JAMA Oncol 2:104–11
    [Google Scholar]
  88. 86.
    Scollon S, Anglin AK, Thomas M, Turner JT, Wolfe Schneider K 2017. A comprehensive review of pediatric tumors and associated cancer predisposition syndromes. J. Genet. Couns. 26:387–434
    [Google Scholar]
  89. 87.
    Sestini R, Bacci C, Provenzano A, Genuardi M, Papi L 2008. Evidence of a four-hit mechanism involving SMARCB1 and NF2 in schwannomatosis-associated schwannomas. Hum. Mutat. 29:227–31
    [Google Scholar]
  90. 88.
    Shah S, Schrader KA, Waanders E, Timms AE, Vijai J et al. 2013. A recurrent germline PAX5 mutation confers susceptibility to pre–B cell acute lymphoblastic leukemia. Nat. Genet. 45:1226–31
    [Google Scholar]
  91. 89.
    Sherborne AL, Hosking FJ, Prasad RB, Kumar R, Koehler R et al. 2010. Variation in CDKN2A at 9p21.3 influences childhood acute lymphoblastic leukemia risk. Nat. Genet. 42:492–94
    [Google Scholar]
  92. 90.
    Slade I, Murray A, Hanks S, Kumar A, Walker L et al. 2011. Heterogeneity of familial medulloblastoma and contribution of germline PTCH1 and SUFU mutations to sporadic medulloblastoma. Fam. Cancer 10:337–42
    [Google Scholar]
  93. 91.
    Smith MJ, O'Sullivan J, Bhaskar SS, Hadfield KD, Poke G et al. 2013. Loss-of-function mutations in SMARCE1 cause an inherited disorder of multiple spinal meningiomas. Nat. Genet. 45:295–98
    [Google Scholar]
  94. 92.
    Tabori U, Hansford JR, Achatz MI, Kratz CP, Plon SE et al. 2017. Clinical management and tumor surveillance recommendations of inherited mismatch repair deficiency in childhood. Clin. Cancer Res. 23:e32–37
    [Google Scholar]
  95. 93.
    Tauziede-Espariat A, Parfait B, Besnard A, Lacombe J, Pallud J et al. 2018. Loss of SMARCE1 expression is a specific diagnostic marker of clear cell meningioma: a comprehensive immunophenotypical and molecular analysis. Brain Pathol 28:466–74
    [Google Scholar]
  96. 94.
    Tolbert VP, Coggins GE, Maris JM 2017. Genetic susceptibility to neuroblastoma. Curr. Opin. Genet. Dev. 42:81–90
    [Google Scholar]
  97. 95.
    Topka S, Vijai J, Walsh MF, Jacobs L, Maria A et al. 2015. Germline ETV6 mutations confer susceptibility to acute lymphoblastic leukemia and thrombocytopenia. PLOS Genet 11:e1005262
    [Google Scholar]
  98. 96.
    Trevino LR, Yang W, French D, Hunger SP, Carroll WL et al. 2009. Germline genomic variants associated with childhood acute lymphoblastic leukemia. Nat. Genet. 41:1001–5
    [Google Scholar]
  99. 97.
    Tsurusaki Y, Okamoto N, Ohashi H, Kosho T, Imai Y et al. 2012. Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome. Nat. Genet. 44:376–78
    [Google Scholar]
  100. 98.
    Turnbull C, Perdeaux ER, Pernet D, Naranjo A, Renwick A et al. 2012. A genome-wide association study identifies susceptibility loci for Wilms tumor. Nat. Genet. 44:681–84
    [Google Scholar]
  101. 99.
    Versteege I, Sevenet N, Lange J, Rousseau-Merck MF, Ambros P et al. 1998. Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature 394:203–6
    [Google Scholar]
  102. 100.
    Vijayakrishnan J, Kumar R, Henrion MY, Moorman AV, Rachakonda PS et al. 2017. A genome-wide association study identifies risk loci for childhood acute lymphoblastic leukemia at 10q26.13 and 12q23.1. Leukemia 31:573–79
    [Google Scholar]
  103. 101.
    Vijayakrishnan J, Studd J, Broderick P, Kinnersley B, Holroyd A et al. 2018. Genome-wide association study identifies susceptibility loci for B-cell childhood acute lymphoblastic leukemia. Nat. Commun. 9:1340
    [Google Scholar]
  104. 102.
    Wakefield CE, Quinn VF, Fardell JE, Signorelli C, Tucker KM et al. 2017. Family history-taking practices and genetic confidence in primary and tertiary care providers for childhood cancer survivors. Pediatr. Blood Cancer 65:e26923
    [Google Scholar]
  105. 103.
    Waszak SM, Northcott PA, Buchhalter I, Robinson GW, Sutter C et al. 2018. Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort. Lancet Oncol 19:785–98
    [Google Scholar]
  106. 104.
    Weintraub M, Lin AY, Franklin J, Tucker MA, Magrath IT, Bhatia KG 1996. Absence of germline p53 mutations in familial lymphoma. Oncogene 12:687–91
    [Google Scholar]
  107. 105.
    Wiemels JL, Walsh KM, de Smith AJ, Metayer C, Gonseth S et al. 2018. GWAS in childhood acute lymphoblastic leukemia reveals novel genetic associations at chromosomes 17q12 and 8q24.21. Nat. Commun. 9:286
    [Google Scholar]
  108. 106.
    Wiemels JL, Wrensch M, Claus EB 2010. Epidemiology and etiology of meningioma. J. Neurooncol. 99:307–14
    [Google Scholar]
  109. 107.
    Witkowski L, Goudie C, Foulkes WD, McCluggage WG 2016. Small-cell carcinoma of the ovary of hypercalcemic type (malignant rhabdoid tumor of the ovary): a review with recent developments on pathogenesis. Surg. Pathol. Clin. 9:215–26
    [Google Scholar]
  110. 108.
    Xu H, Cheng C, Devidas M, Pei D, Fan Y et al. 2012. ARID5B genetic polymorphisms contribute to racial disparities in the incidence and treatment outcome of childhood acute lymphoblastic leukemia. J. Clin. Oncol. 30:751–57
    [Google Scholar]
  111. 109.
    Xu H, Yang W, Perez-Andreu V, Devidas M, Fan Y et al. 2013. Novel susceptibility variants at 10p12.31–12.2 for childhood acute lymphoblastic leukemia in ethnically diverse populations. J. Natl. Cancer Inst. 105:733–42
    [Google Scholar]
  112. 110.
    Yang Y, Muzny DM, Xia F, Niu Z, Person R et al. 2014. Molecular findings among patients referred for clinical whole-exome sequencing. JAMA 312:1870–79
    [Google Scholar]
  113. 111.
    Yasmin N, Bauer T, Modak M, Wagner K, Schuster C et al. 2013. Identification of bone morphogenetic protein 7 (BMP7) as an instructive factor for human epidermal Langerhans cell differentiation. J. Exp. Med. 210:2597–610
    [Google Scholar]
  114. 112.
    Zhang J, Walsh MF, Wu G, Edmonson MN, Gruber TA et al. 2015. Germline mutations in predisposition genes in pediatric cancer. N. Engl. J. Med. 373:2336–46
    [Google Scholar]
  115. 113.
    Zhang MY, Churpek JE, Keel SB, Walsh T, Lee MK et al. 2015. Germline ETV6 mutations in familial thrombocytopenia and hematologic malignancy. Nat. Genet. 47:180–85
    [Google Scholar]
/content/journals/10.1146/annurev-genom-083118-015415
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  • Article Type: Review Article
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