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Molecular Pathology and Diagnostics of Childhood Tumors

  • Enid Gilbert-BarnessEmail author
  • Kristen Eisbrenner
Chapter
Part of the Cancer Growth and Progression book series (CAGP, volume 16)

Abstract

Neoplasms in the fetus and infant are discussed in reference to types, incidence, clinical features, behavior, and response to treatment. Tumors that occur predominately in the first year of life have certain features of embryonic growth, including Wilms’ tumors, neuroblastomas, embryonic sarcomas, yolk sac tumors of the testis, hepatoblastomas, and medulloblastomas of the brain, as well as sacrococcygeal tumors that have an overgrowth of embryonic components. Chromosome translocations, tumor suppressor genes, and some syndromes and congenital malformations associated with childhood tumors are discussed.

Keywords

Childhood tumors Molecular Genetic Chromosome abnormalities 

Abbreviations

ARMS

Alveolar rhabdomyosarcoma

BWS

Beckwith-Wiedemann syndrome

CHEK2

Checkpoint kinase 2

CN

Cystic nephroma

CNS

Central nervous system

ERMS

Embryonal rhabdomyosarcoma

EWS

Ewing sarcoma

FAP

Familial adenomatous polyposis

FISH

Fluorescent in situ hybridization

GIST

Gastrointestinal stromal tumors

HPV

Human papilloma virus

IGF2

Insulin-like growth factor II

MEN1

Multiple endocrine neoplasia type 1

MEN2

Multiple endocrine neoplasia type 2

NF1

Neurofibromatosis type 1

NF2

Neurofibromatosis type 2

PDGF

Platelet-derived growth factor

PNET

Primitive neuroectodermal tumor

PTCH

Patch

RT-PCR

Reverse transcription-polymerase chain reaction

SHH

Sonic hedgehog

SMO

Smoothened

VHL

Von Hippel-Lindau

WAGR syndrome

Wilms’ tumor, aniridia, genitourinary abnormalities and mental retardation

WT-1

Wilms’ tumor-1 gene product

References

  1. 1.
    Bader JL, Miller RW (1979) US cancer incidence and mortality in the first year of life. Am J Dis Child 133:157–159PubMedGoogle Scholar
  2. 2.
    Bolande RP (1971) Benignity of neonatal tumors and concept of cancer repression in early life. Am J Dis Child 122:12–14PubMedGoogle Scholar
  3. 3.
    Bolande RP (1976) Neoplasia of early life and its relationships to teratogenesis. Perspect Pediatr Pathol 3:145–183PubMedGoogle Scholar
  4. 4.
    Crist W, Pullen J, Boyett J, Falletta J, van Eys J, Borowitz M, Jackson J, Dowell B, Frankel L, Quddus F et al (1986) Clinical and biologic features predict a poor prognosis in acute lymphoid leukemias in infants: a Pediatric Oncology Group Study. Blood 67:135–140PubMedGoogle Scholar
  5. 5.
    Young JL Jr, Ries LG, Silverberg E, Horm JW, Miller RW (1986) Cancer incidence, survival, and mortality for children younger than age 15 years. Cancer 58(2 Suppl):598–602PubMedCrossRefGoogle Scholar
  6. 6.
    Gilbert-Barness E (ed) (2007) Potter’s pathology of the fetus, infant and child, 2nd edn. Mosby-Elsevier, PhiladelphiaGoogle Scholar
  7. 7.
    Reaman G (1993) Special considerations for the infant with cancer, 2nd edn. Lippincott, PhiladelphiaGoogle Scholar
  8. 8.
    Reaman G, Zeltzer P, Bleyer WA, Amendola B, Level C, Sather H, Hammond D (1985) Acute lymphoblastic leukemia in infants less than one year of age: a cumulative experience of the Children's Cancer Study Group. J Clin Oncol 3:1513–1521PubMedGoogle Scholar
  9. 9.
    Willis RA (1962) The borderland of embryology and pathology. Butterworths, LondonGoogle Scholar
  10. 10.
    Fernbach DJ, Vietti TJ (1991) General aspects of childhood cancer, 3rd edn. Mosby, St. LouisGoogle Scholar
  11. 11.
    Isaacs HJ (1993) Tumors of the fetus and infant-an atlas. Springer, New YorkGoogle Scholar
  12. 12.
    Berry PJ (1993) Congenital tumors, 2nd edn. Springer, BerlinGoogle Scholar
  13. 13.
    Broadbent VA (1992) Malignant disease in the neonate, 2nd edn. Churchill Livingstone, EdinburghGoogle Scholar
  14. 14.
    Gale GB, D'Angio GJ, Uri A, Chatten J, Koop CE (1982) Cancer in neonates: the experience at the children’s hospital of Philadelphia. Pediatrics 70:409–413PubMedGoogle Scholar
  15. 15.
    Isaacs H Jr (1983) Neoplasms in infants: a report of 265 cases. Pathol Annu 18(Pt 2):165–214PubMedGoogle Scholar
  16. 16.
    Werb P, Scurry J, Ostor A, Fortune D, Attwood H (1992) Survey of congenital tumors in perinatal necropsies. Pathology 24:247–253PubMedCrossRefGoogle Scholar
  17. 17.
    Mulvihill JJ (1993) Childhood cancer environment and hereditary, 2nd edn. JB Lippincott, PhiladelphiaGoogle Scholar
  18. 18.
    Isaacs H Jr (2007) Introduction to tumors. In: Gilbert-Barness E (ed) Potter’s pathology of fetus, infant and child, 2nd edn. Elsevier, PhiladelphiaGoogle Scholar
  19. 19.
    Isaacs H Jr (1997) Tumors. In: Gilbert-Barness E (ed) Potter’s pathology of fetus, infant and child. Mosby Year Book, PhiladelphiaGoogle Scholar
  20. 20.
    Lengauer C (2003) Cancer. An unstable liaison. Science 300:442–443PubMedCrossRefGoogle Scholar
  21. 21.
    Kinzler KW, Vogelstein B (2001) Familial cancer syndromes the role of caretakers an gatekeepers, 8th edn. McGraw-Hill, New YorkGoogle Scholar
  22. 22.
    Feinberg AP (2004) The epigenetics of cancer etiology. Semin Cancer Biol 14:427–432PubMedCrossRefGoogle Scholar
  23. 23.
    Falls JG, Pulford DJ, Wylie AA, Jirtle RL (1999) Genomic imprinting: implications for human disease. Am J Pathol 154:635–647PubMedCrossRefGoogle Scholar
  24. 24.
    Hall JG (1990) Genomic imprinting: review and relevance to human diseases. Am J Hum Genet 46:857–873PubMedGoogle Scholar
  25. 25.
    Hark AT, Schoenherr CJ, Katz DJ, Ingram RS, Levorse JM, Tilghman SM (2000) CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus. Nature 405:486–489PubMedCrossRefGoogle Scholar
  26. 26.
    Barlow DP (1994) Imprinting: a gamete’s point of view. Trends Genet 1994(10):194–199CrossRefGoogle Scholar
  27. 27.
    Villavicencio EH, Walterhouse DO, Iannaccone PM (2000) The sonic hedgehog-patched-gli pathway in human development and disease. Am J Hum Genet 67:1047–1054PubMedGoogle Scholar
  28. 28.
    Hooper JE, Scott MP (2005) Communicating with hedgehogs. Nat Rev Mol Cell Biol 6:306–317PubMedCrossRefGoogle Scholar
  29. 29.
    Yuspa SH, Epstein EH Jr (2005) Cancer. An anchor for tumor cell invasion. Science 307:1727–1728PubMedCrossRefGoogle Scholar
  30. 30.
    Meder D, Simons K (2005) Cell biology. Ras on the roundabout. Science 307:1731–1733PubMedCrossRefGoogle Scholar
  31. 31.
    Fodde R, Smits R (2002) Cancer biology. A matter of dosage. Science 298:761–763PubMedCrossRefGoogle Scholar
  32. 32.
    Wilkin F, Gagne N, Paquette J, Oligny LL, Deal C (2000) Pediatric adrenocortical tumors: molecular events leading to insulin-like growth factor II gene overexpression. J Clin Endocrinol Metab 85:2048–2056PubMedCrossRefGoogle Scholar
  33. 33.
    Grier DG, Thompson A, Kwasniewska A, McGonigle GJ, Halliday HL, Lappin TR (2005) The pathophysiology of HOX genes and their role in cancer. J Pathol 205:154–171PubMedCrossRefGoogle Scholar
  34. 34.
    Levine AJ (1997) p53, the cellular gatekeeper for growth and division. Cell 88:323–331PubMedCrossRefGoogle Scholar
  35. 35.
    Guo W, Giancotti FG (2004) Integrin signaling during tumour progression. Nat Rev Mol Cell Biol 5:816–826PubMedCrossRefGoogle Scholar
  36. 36.
    Knudson AG Jr (1986) Genetics of human cancer. Annu Rev Genet 20:231–251PubMedCrossRefGoogle Scholar
  37. 37.
    Cooper WN, Luharia A, Evans GA, Raza H, Haire AC, Grundy R, Bowdin SC, Riccio A, Sebastio G, Bliek J et al (2005) Molecular subtypes and phenotypic expression of Beckwith-Wiedemann syndrome. Eur J Hum Genet 13:1025–1032PubMedCrossRefGoogle Scholar
  38. 38.
    DeBaun MR, Niemitz EL, McNeil DE, Brandenburg SA, Lee MP, Feinberg AP (2002) Epigenetic alterations of H19 and LIT1 distinguish patients with Beckwith-Wiedemann syndrome with cancer and birth defects. Am J Hum Genet 70:604–611PubMedCrossRefGoogle Scholar
  39. 39.
    McTaggart SJ, Algar E, Chow CW, Powell HR, Jones CL (2001) Clinical spectrum of Denys-Drash and Frasier syndrome. Pediatr Nephrol 16:335–339PubMedCrossRefGoogle Scholar
  40. 40.
    Pelletier J, Bruening W, Kashtan CE, Mauer SM, Manivel JC, Striegel JE, Houghton DC, Junien C, Habib R, Fouser L et al (1991) Germline mutations in the Wilms’ tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome. Cell 67:437–447PubMedCrossRefGoogle Scholar
  41. 41.
    Porteus MH, Narkool P, Neuberg D, Guthrie K, Breslow N, Green DM, Diller L (2000) Characteristics and outcome of children with Beckwith-Wiedemann syndrome and Wilms’ tumor: a report from the National Wilms Tumor Study Group. J Clin Oncol 18:2026–2031PubMedGoogle Scholar
  42. 42.
    Call KM, Glaser T, Ito CY, Buckler AJ, Pelletier J, Haber DA, Rose EA, Kral A, Yeger H, Lewis WH et al (1990) Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms’ tumor locus. Cell 60:509–520PubMedCrossRefGoogle Scholar
  43. 43.
    Haber DA, Englert C, Maheswaran S (1996) Functional properties of WT1. Med Pediatr Oncol 27:453–455PubMedCrossRefGoogle Scholar
  44. 44.
    Gessler M, Poustka A, Cavenee W, Neve RL, Orkin SH, Bruns GA (1990) Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping. Nature 343:774–778PubMedCrossRefGoogle Scholar
  45. 45.
    Gashler AL, Bonthron DT, Madden SL, Rauscher FJ 3rd, Collins T, Sukhatme VP (1992) Human platelet-derived growth factor A chain is transcriptionally repressed by the Wilms tumor suppressor WT1. Proc Natl Acad Sci USA 89:10984–10988PubMedCrossRefGoogle Scholar
  46. 46.
    Drummond IA, Madden SL, Rohwer-Nutter P, Bell GI, Sukhatme VP, Rauscher FJ 3rd (1992) Repression of the insulin-like growth factor II gene by the Wilms tumor suppressor WT1. Science 257:674–678PubMedCrossRefGoogle Scholar
  47. 47.
    Morrison DJ, English MA, Licht JD (2005) WT1 induces apoptosis through transcriptional regulation of the proapoptotic Bcl-2 family member Bak. Cancer Res 65:8174–8182PubMedCrossRefGoogle Scholar
  48. 48.
    Scott J, Cowell J, Robertson ME, Priestley LM, Wadey R, Hopkins B, Pritchard J, Bell GI, Rall LB, Graham CF et al (1985) Insulin-like growth factor-II gene expression in Wilms’ tumour and embryonic tissues. Nature 317:260–262PubMedCrossRefGoogle Scholar
  49. 49.
    Fraizer GE, Bowen-Pope DF, Vogel AM (1987) Production of platelet-derived growth factor by cultured Wilms’ tumor cells and fetal kidney cells. J Cell Physiol 133:169–174PubMedCrossRefGoogle Scholar
  50. 50.
    Eccles MR, Wallis LJ, Fidler AE, Spurr NK, Goodfellow PJ, Reeve AE (1992) Expression of the PAX2 gene in human fetal kidney and Wilms’ tumor. Cell Growth Differ 3:279–289PubMedGoogle Scholar
  51. 51.
    Little MH, Prosser J, Condie A, Smith PJ, Van Heyningen V, Hastie ND (1992) Zinc finger point mutations within the WT1 gene in Wilms tumor patients. Proc Natl Acad Sci USA 89:4791–4795PubMedCrossRefGoogle Scholar
  52. 52.
    Feinberg AP (1996) Multiple genetic abnormalities of 11p15 in Wilms’ tumor. Med Pediatr Oncol 27:484–489PubMedCrossRefGoogle Scholar
  53. 53.
    Li M, Squire JA, Weksberg R (1997) Molecular genetics of Beckwith-Wiedemann syndrome. Curr Opin Pediatr 9:623–629PubMedCrossRefGoogle Scholar
  54. 54.
    Huff V, Amos CI, Douglass EC, Fisher R, Geiser CF, Krill CE, Li FP, Strong LC, McDonald JM (1997) Evidence for genetic heterogeneity in familial Wilms’ tumor. Cancer Res 57:1859–1862PubMedGoogle Scholar
  55. 55.
    Rahman N, Abidi F, Ford D, Arbour L, Rapley E, Tonin P, Barton D, Batcup G, Berry J, Cotter F et al (1998) Confirmation of FWT1 as a Wilms’ tumour susceptibility gene and phenotypic characteristics of Wilms’ tumour attributable to FWT1. Hum Genet 103:547–556PubMedCrossRefGoogle Scholar
  56. 56.
    Gilbert-Barness EF (ed) (1998) Potter’s atlas of developmental and infant pathology. Mosby Year Book, PhiladelphiaGoogle Scholar
  57. 57.
    Sebire NJ, Malone M, Ashworth M, Jacques TS (2010) Diagnostic pediatric surgical pathology. Churchill-Livingstone/Elsevier, PhiladelphiaGoogle Scholar
  58. 58.
    Argani P, Fritsch M, Kadkol SS, Schuster A, Beckwith JB, Perlman EJ (2000) Detection of the ETV6-NTRK3 chimeric RNA of infantile fibrosarcoma/cellular congenital mesoblastic nephroma in paraffin-embedded tissue: application to challenging pediatric renal stromal tumors. Mod Pathol 13:29–36PubMedCrossRefGoogle Scholar
  59. 59.
    Schwab M, Westermann F, Hero B, Berthold F (2003) Neuroblastoma: biology and molecular and chromosomal pathology. Lancet Oncol 4:472–480PubMedCrossRefGoogle Scholar
  60. 60.
    Ara T, DeClerck YA (2006) Mechanisms of invasion and metastasis in human neuroblastoma. Cancer Metastasis Rev 25:645–657PubMedCrossRefGoogle Scholar
  61. 61.
    Lastowska M, Cullinane C, Vriend S, Cotterill S, Brown N, O’Neill S, Mazzocco K, Roberts P, Nicholson J, Ellershaw C, Pearson AD, Jackson MS, United Kingdom Children Cancer Study Group and the United Kingdom Cancer Cytogenetics Group (2001) Comprehensive genetic and histopathologic study reveals three types of neuroblastoma tumors. J Clin Oncol 19:3080–3090PubMedGoogle Scholar
  62. 62.
    Shimada H (2003) The international neuroblastoma pathology classification. Pathologica 95:240–241PubMedGoogle Scholar
  63. 63.
    Gilbert-Barness E (2007) Potter’s pathology of the fetus, infant and child, vol 1 and 2, 2nd edn. Elsevier, PhiladelphiaGoogle Scholar
  64. 64.
    Peuchmaur M, d’Amore ES, Joshi W, Hata J, Roald B, Dehner LP, Gerbing RB, Stram DO, Lukens JN, Matthay KK, Shimada H (2003) Revision of the international neuroblastoma pathology classification: confirmation of favorable and unfavorable prognostic subsets in ganglioneuroblastoma, nodular. Cancer 98:2274–2281PubMedCrossRefGoogle Scholar
  65. 65.
    Lakhani VT, You YN, Wells SA (2007) The multiple endocrine neoplasia syndromes. Annu Rev Med 58:253–265PubMedCrossRefGoogle Scholar
  66. 66.
    Tognon C, Knezevich SR, Huntsman D et al (2002) Expression of the ETV6-NTRK3 gene fusion as a primary event in human secretory breast carcinoma. Cancer Cell 2:367–376PubMedCrossRefGoogle Scholar
  67. 67.
    Rajan PB, Cranor ML, Rosen PP (1998) Cytosarcoma phyllodes in adolescent girls and young women: a study of 45 patients. Am J Surg Pathol 22:64–69PubMedCrossRefGoogle Scholar
  68. 68.
    Barrio AV, Clark BD, Goldberg JI et al (2007) Clinicopathologic features and long-term outcomes of 293 phyllodes tumors of the breast. Ann Surg Oncol 14:2961–2970PubMedCrossRefGoogle Scholar
  69. 69.
    Pelizzo G, Conoscenti G, Kalache KD et al (2003) Antenatal manifestation of congenital pancreatoblastoma in a fetus with Beckwith-Wiedemann syndrome. Prenat Diagn 23:292–294PubMedCrossRefGoogle Scholar
  70. 70.
    Eberhart CG, Kepner JL, Goldthwaite PT et al (2004) Histopathological and molecular prognostic markers in medulloblastoma: c-myc, N-myc, TrkC, and anaplasia. J Neuropathol Exp Neurol 63:441–449PubMedGoogle Scholar
  71. 71.
    Lamont JM, McManamy CS, Pearson AD, Clifford SC, Ellison DW (2004) Combined histopathological and molecular cytogenetic stratification of medulloblastoma patients. Clin Cancer Res 10:5482–5493PubMedCrossRefGoogle Scholar
  72. 72.
    Isaacs H Jr (1997) Tumors. In: Gilbert-Barness EF (ed) Potter’s pathology of the fetus and infant. Mosby Year Book, PhiladelphiaGoogle Scholar
  73. 73.
    Ping AJ, Reeve AE, Law DJ, Young MR, Boehnke M, Feinberg AP (1989) Genetic linkage of Beckwith-Wiedemann syndrome to 11p15. Am J Hum Genet 44:720–723PubMedGoogle Scholar
  74. 74.
    Wu NF, Kushnick T (1974) The Beckwith-Wiedemann syndrome. The exomphalos-macroglossia-gigantism syndrome. Clin Pediatr (Phila) 13:452–457CrossRefGoogle Scholar
  75. 75.
    Henry I, Bonaiti-Pellie C, Chehensse V, Beldjord C, Schwartz C, Utermann G, Junien C (1991) Uniparental paternal disomy in a genetic cancer-predisposing syndrome. Nature 351:665–667PubMedCrossRefGoogle Scholar
  76. 76.
    Dao D, Walsh CP, Yuan L, Gorelov D, Feng L, Hensle T, Nisen P, Yatnashiro DJ, Bestor TH, Tycko B (1999) Multipoint analysis of human chromosome 11p15/mouse digital chromosome 7: inclusion of H19/IGF2 in the minimal WT2 region, gene specificity of H19 silencing in Wilms’ tumorigenesis and methylation hyper-dependence of H19 imprinting. Hum Mol Genet 8:1337–1352PubMedCrossRefGoogle Scholar
  77. 77.
    Lee MP, DeBaun MR, Mitsuya K, Galonek HL, Brandenburg S, Oshimura M, Feinberg AP (1999) Loss of imprinting of a paternally expressed transcript, with antisense orientation to KVLQT1, occurs frequently in Beckwith-Wiedemann syndrome and is independent of insulin-like growth factor II imprinting. Proc Natl Acad Sci USA 96:5203–5208PubMedCrossRefGoogle Scholar
  78. 78.
    Morison IM, Reeve AE (1998) A catalogue of imprinted genes and parent-of-origin effects in humans and animals. Hum Mol Genet 7:1599–1609PubMedCrossRefGoogle Scholar
  79. 79.
    Onyango P, Miller W, Lehoczky J, Leung CT, Birren B, Wjeelan S, Dewar K, Feinberg AP (2000) Sequence and comparative analysis of the mouse 1-megabase region orthologous to the human 11p15 imprinted domain. Genome Res 10:1697–1710PubMedCrossRefGoogle Scholar
  80. 80.
    Paulsen M, Davies KR, Bowden LM, Villar AJ, Franck I, Fuermann M, Dean WL, Moore TF, Rodrigues N, Davies KE et al (1998) Syntenic organization of the mouse distal chromosome 8 imprinting cluster and the Beckwith-Wiedemann syndrome region in chromosome 11p15.5. Hum Mol Genet 7:1149–1159PubMedCrossRefGoogle Scholar
  81. 81.
    Xin Z, Soejima H, Higashimoto K, Yatsuki H, Zhu X, Satoh Y, Miasaki Z, Kaneko Y, Jimo Y, Fukuzawa R et al (2000) A novel imprinted gene, KCNQ1DN, within the WT2 critical region of human chromosome 11p15.5 and its reduced expression in Wilms’ tumors. J Biochem (Toyko) 128:847–853CrossRefGoogle Scholar
  82. 82.
    Seizinger BR, Rouleau GA, Ozelius LJ, Lane AH, Faryniarz AG, Chao MV, Huson S, Korf BR, Parry DM, Pericak-Vance MA et al (1987) Genetic linkage of von Recklinghausen neurofibromatosis to the nerve growth factor receptor gene. Cell 49:589–594PubMedCrossRefGoogle Scholar
  83. 83.
    Listernick R, Charrow J, Gutmann DH (1999) Intracranial gliomas in neurofibromatosis type 1. Am J Med Genet 89:38–44PubMedCrossRefGoogle Scholar
  84. 84.
    Evans DG, Birch JM, Ramsden RT (1999) Paediatric presentation of type 2 neurofibromatosis. Arch Dis Child 81:496–499PubMedCrossRefGoogle Scholar
  85. 85.
    Brook-Carter PT, Peral B, Ward CJ, Thompson P, Hughes J, Maheshwar MM, Nellist M, Gamble V, Harris PC, Sampson JR (1994) Deletion of the TSC2 and PKD1 genes associated with severe infantile polycystic kidney disease-a contiguous gene syndrome. Nat Genet 8:328–332PubMedCrossRefGoogle Scholar
  86. 86.
    Crino PB, Nathanson KL, Henskie EP (2006) The tuberous sclerosis complex. N Engl J Med 355:1345–1356PubMedCrossRefGoogle Scholar
  87. 87.
    Vinaitheerthan M, Wei J, Mizuguchi M, Greco A, Barness EG (2004) Tuberous sclerosis: immunohistochemistry expression of tuberin and hamartin in a 31-week gestational fetus. Fetal Pediatr Pathol 23:241–249PubMedCrossRefGoogle Scholar
  88. 88.
    Cavenee WK (1997) Turcot syndrome. International Agency for Research on Cancer, LyonGoogle Scholar
  89. 89.
    Schofield D, West DC, Anthony DC, Marshal R, Sklar J (1995) Correlation of loss of heterozygosity at chromosome 9q with histological subtype in medulloblastomas. Am J Pathol 146:472–480PubMedGoogle Scholar
  90. 90.
    Cowan R, Hoban P, Kelsey A, Birch JM, Gattamaneni R, Evans DG (1997) The gene for the nevoid basal cell carcinoma syndrome acts as a tumour-suppressor gene in medulloblastoma. Br J Cancer 76:141–145PubMedCrossRefGoogle Scholar
  91. 91.
    Wiestler OD, Kleihues P, Vital A, Padberg GW (1997) Cowden disease and dysplastic gangliocytoma of the cerebellum/Lhermitte-Duclos disease. International Agency for Research on Cancer, LyonGoogle Scholar
  92. 92.
    Marsh D, Zori R (2002) Genetic insights into familial cancers-update and recent discoveries. Cancer Lett 181:125–164PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  1. 1.Department of Pathology and Cell Biology, Pediatrics and Obstetrics and GynecologyUniversity of South Florida College of Medicine at Tampa General HospitalTampaUSA
  2. 2.University of South Florida College of Medicine at Tampa General HospitalTampaUSA

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