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The Biology of AYA Cancers

  • James V. Tricoli
  • Archie Bleyer
  • Jakob Anninga
  • Ronald Barr
Chapter
Part of the Pediatric Oncology book series (PEDIATRICO)

Abstract

Investigating the potential biological basis of age-related differences in outcome for AYA with cancer could lead to a better understanding of the biology, facilitate the development of new diagnostic and predictive markers, and identify novel therapeutic targets and treatment approaches for AYA patients. The evidence that cancers in AYA patients may differ biologically from those in older and younger populations includes data from numerous laboratories. However, much of this evidence is preliminary, and large comprehensive studies to confirm and validate these findings are only now beginning to get underway. Indeed, there may be substantial differences in biological and molecular features between different age groups even within the population of AYA patients with a specific cancer type. If age is a good surrogate for a unique tumor biology associated with AYA cancers, then studies of cancers in AYA patients will almost certainly illuminate alternative tumorigenic pathways and will also likely benefit patients in other age groups whose tumors exhibit similar biological/molecular features. The biologic, molecular, and clinical features of five AYA cancers (colon, breast, acute lymphoblastic leukemia, melanoma, and sarcoma) are highlighted in this chapter, and the current state of research for each of them is examined. What will be required to better diagnose, treat, and predict response in patients with AYA cancer is also discussed.

Keywords

Acute Lymphoblastic Leukemia Synovial Sarcoma Malignant Peripheral Nerve Sheath Tumor Ewing Sarcoma Alveolar Soft Part Sarcoma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

Cary K. Anders, M.D.

Associate Professor of Medicine

Division of Hematology Oncology

University of North Carolina at Chapel Hill

Lineberger Comprehensive Cancer Center

Chapel Hill, NC 27599

Donald G. Blair, Ph.D.

Division of Cancer Biology

National Cancer Institute

9609 Medical Center Drive

Rockville, M.D. 20892

Lisa A. Boardman, M.D.

Professor of Medicine

Mayo Clinic College of Medicine

200 First Street SW

Rochester, MN 55906

Brandon Hayes-Lattin, M.D., F.A.C.P.

Associate Professor of Medicine

Medical Director, Adolescent and Young Adult (AYA) Oncology Program

Division of Hematology and Medical Oncology

Knight Cancer Institute

Oregon Health and Science University

3181 SW Sam Jackson Park Road

Portland, OR 97239

Stephan P. Hunger, M.D.

Chief, Division of Oncology

Director, Center for Childhood Cancer Research

Children’s Hospital of Philadelphia

3501 Civic Center Boulevard, CTRB#3060

Philadelphia, PA 19104

Javed Khan, M.D.

Deputy Chief, Genetics Branch

Center for Cancer Research

National Cancer Institute

Pediatric Oncology Branch

Bethesda, M.D. 20892

Shivaani Kummar, M.D.

Professor of Medicine

Director, Phase I Clinical Research ProgramStanford University School of Medicine

780 Welch Road,

Room CJ250L

Palo Alto, CA 94304

Melinda Merchant, M.D., Ph.D.

Center for Cancer Research

National Cancer Institute

Pediatric Oncology Branch

Bethesda, M.D. 20892

Nita L. Seibel, M.D.

Cancer Therapy Evaluation Program

Division of Cancer Treatment and Diagnosis

National Cancer Institute

9609 Medical Center Drive

Rockville, M.D. 20892

Magdalena Thurin, Ph.D.

Cancer Diagnosis Program

Division of Cancer Treatment and Diagnosis

National Cancer Institute

9609 Medical Center Drive

Rockville, M.D. 20892

Cheryl Willman, M.D.

The Maurice and Marguerite Liberman Distinguished Chair in Cancer Research

Professor of Pathology

University of New Mexico School of Medicine Director and CEO

University of New Mexico Cancer Center

1201 Camino de Salud NE

Albuquerque, NM 87131

References

  1. 1.
    Tricoli JV, Seibel NL, Blair DG et al (2011) Unique characteristics of adolescent and young adult acute lymphoblastic leukemia, breast cancer, and colon cancer. J Natl Cancer Inst 103:628–635CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Bleyer A, Barr R, Hayes-Lattin B et al (2008) The distinctive biology of cancer in adolescents and young adults. Nat Rev Cancer 8:288–298CrossRefPubMedGoogle Scholar
  3. 3.
    Liu B, Farrington SM, Petersen GM et al (1995) Genetic instability occurs in the majority of young patients with colorectal cancer. Nat Med 1:348–352CrossRefPubMedGoogle Scholar
  4. 4.
    Liang JT, Huang KC, Cheng AL et al (2003) Clinicopathological and molecular biological features of colorectal cancer in patients less than 40 years of age. Br J Surg 90:205–214CrossRefPubMedGoogle Scholar
  5. 5.
    Hill DA, Furman WL, Billups CA et al (2007) Colorectal carcinoma in childhood and adolescence: a clinicopathologic review. J Clin Oncol 25:5808–5814CrossRefPubMedGoogle Scholar
  6. 6.
    Ziadi S, Ksiaa F, Ben Gacem R, Labaied N, Mokni M, Trimeche M (2014) Clinicopathologic characteristics of colorectal cancer with microsatellite instability. Pathol Res Pract 210:98–104CrossRefPubMedGoogle Scholar
  7. 7.
    Anders CK, Fan C, Parker JS et al (2011) Breast carcinomas arising at a young age: unique biology or a surrogate for aggressive intrinsic subtypes? J Clin Oncol 29:e18–e20CrossRefPubMedGoogle Scholar
  8. 8.
    Surveillance, epidemiology, and end results (SEER) program (www.seer.cancer.gov) SEER*Stat Database: incidence – SEER 18 Regs research data + Hurricane Katrina impacted Louisiana cases, Nov 2014 Sub (2000–2012) < Katrina/Rita population adjustment >−linked to county attributes – total U.S., 1969–2013 counties, National Cancer Institute, DCCPS, Surveillance Research Program, Surveillance Systems Branch, released Apr 2015, based on the Nov 2014 submission
  9. 9.
    Ribnikar D, Ribeiro JM, Pinto D, Sousa B, Pinto AC, Gomes E, Moser EC, Cardoso MJ, Cardoso F (2015) Breast cancer under age 40: a different approach. Curr Treat Options Oncol 16(4):16CrossRefPubMedGoogle Scholar
  10. 10.
    Peng R, Wang S, Shi Y et al (2011) Patients 35 years old or younger with operable breast cancer are more at risk for relapse and survival: a retrospective matched case-control study. Breast 20:568–573CrossRefPubMedGoogle Scholar
  11. 11.
    Cancello G, Maisonneuve P, Rotmensz N et al (2010) Prognosis and adjuvant treatment effects in selected breast cancer subtypes of very young women (<35 years) with operable breast cancer. Ann Oncol 21:1974–1981CrossRefPubMedGoogle Scholar
  12. 12.
    Keegan TH, DeRouen MC, Press DJ, Kurian AW et al (2012) Occurrence of breast cancer subtypes in adolescent and young adult women. Breast Cancer Res 14:R55CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Mullighan CG, Willman CL (2011) Advances in the biology of acute lymphoblastic leukemia – from genomics to the clinic. J Adolesc Young Adult Oncol 1:77–86CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Chessells JM, Veys P, Kempski H et al (2003) Long-term follow-up of relapsed childhood acute lymphoblastic leukaemia. Br J Haematol 123:396–405CrossRefPubMedGoogle Scholar
  15. 15.
    Einsiedel HG, von Stackelberg A, Hartmann R et al (2005) Long-term outcome in children with relapsed ALL by risk-stratified salvage therapy: results of trial acute lymphoblastic leukemia-relapse study of the Berlin-Frankfurt-Munster Group 87. J Clin Oncol 23:7942–7950CrossRefPubMedGoogle Scholar
  16. 16.
    Seibel NL, Steinherz PG, Sather HN et al (2008) Early post-induction intensification therapy improves survival for children and adolescents with high-risk acute lymphoblastic leukemia: a report from the Children’s Oncology Group. Blood 111:2548–2555CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Douer D, DeAngelo DJ, Advani A, Arellano M, Litzow M, Damon L, Kovacsovics T, Luger S, Seibel N, Bleyer A (2014) Applying pediatric therapeutic strategies to adults with acute lymphoblastic leukemia and lymphoma. II. Comparison with adult treatment regimens, including hyper-CVAD. Am Oncol Hematol Rev 47–53Google Scholar
  18. 18.
    Howlader N, Noone AM, Krapcho M et al (2012) SEER cancer statistics review, 1975–2010. National Cancer Institute, Bethesda, http://seer.cancer.gov/csr/1975_2010/, based on November 2012 SEER data submission, posted to the SEER web site, April 2013Google Scholar
  19. 19.
    Bleyer A (9 Nov 2011) Exponentially increasing incidence of childhood leukemia in young adults. Chemother Found Symp. NYCGoogle Scholar
  20. 20.
    Harrison CJ (2009) Cytogenetics of paediatric and adolescent acute lymphoblastic leukaemia. Br J Haematol 144:147–156CrossRefPubMedGoogle Scholar
  21. 21.
    Aifantis I, Raetz E, Buonamici S (2008) Molecular pathogenesis of T-cell leukaemia and lymphoma. Nat Rev Immunol 8:380–390CrossRefPubMedGoogle Scholar
  22. 22.
    Pappo AS (2003) Melanoma in children and adolescents. Eur J Cancer 39:2651–2661CrossRefPubMedGoogle Scholar
  23. 23.
    Ferrari A, Bono A, Baldi M et al (2005) Does melanoma behave differently in younger children than in adults? A retrospective study of 33 cases of childhood melanoma from a single institution. Pediatrics 115:649–654CrossRefPubMedGoogle Scholar
  24. 24.
    Sondak VK, Taylor JM, Sabel MS et al (2004) Mitotic rate and younger age are predictors of sentinel lymph node positivity: lessons learned from the generation of a probabilistic model. Ann Surg Oncol 11:247–258CrossRefPubMedGoogle Scholar
  25. 25.
    Livestro DP, Kaine EM, Michaelson JS et al (2007) Melanoma in the young: differences and similarities with adult melanoma: a case-matched controlled analysis. Cancer 110:614–624CrossRefPubMedGoogle Scholar
  26. 26.
    Baldini E, Demetri GD, Fletcher CD, Foran J, Marcus KC, Singer S (1999) Adults with Ewing’s sarcoma/primitive neuroectodermal tumor: adverse effect of older age and primary extraosseous disease on outcome. Ann Surg 230:79–86CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Cotterill SJ, Ahrens S, Paulussen M, Jürgens HF, Voûte PA, Gadner H, Craft AW (2000) Prognostic factors in Ewing’s tumor of bone: analysis of 975 patients from the European Intergroup Cooperative Ewing’s Sarcoma Study Group. J Clin Oncol 18:3108–3114CrossRefPubMedGoogle Scholar
  28. 28.
    Surveillance, Epidemiology, and End Results (SEER) program (www.seer.cancer.gov) SEER*Stat database: mortality – all COD, aggregated with state, total U.S. (1969–2012) <Katrina/Rita population adjustment>, National Cancer Institute, DCCPS, Surveillance Research Program, Surveillance Systems Branch, released Apr 2015. Underlying mortality data provided by NCHS (www.cdc.gov/nchs)
  29. 29.
    Kakar S, Aksoy S, Burgart LJ et al (2004) Mucinous carcinoma of the colon: correlation of loss of mismatch repair enzymes with clinicopathologic features and survival. Mod Pathol 17:696–700CrossRefPubMedGoogle Scholar
  30. 30.
    Durno C, Aronson M, Bapat B et al (2005) Family history and molecular features of children, adolescents, and young adults with colorectal carcinoma. Gut 54:1146–1150CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Sultan I, Rodriguez-Galindo C, El-Taani H et al (2010) Distinct features of colorectal cancer in children and adolescents: a population-based study of 159 cases. Cancer 116:758–765CrossRefPubMedGoogle Scholar
  32. 32.
    Lynch JT, Lynch JF, Lynch PM, Attard T (2008) Hereditary colorectal cancer syndromes: molecular genetics, genetic counseling, diagnosis and management. Fam Cancer 7:27–39CrossRefPubMedGoogle Scholar
  33. 33.
    The Cancer Genome Atlas Network (2012) Comprehensive molecular characterization of human colon and rectal cancer. Nature 487:330–337CrossRefPubMedCentralGoogle Scholar
  34. 34.
    Tricoli JV, Rall LB, Karakousis CP et al (1986) Enhanced levels of insulin-like growth factor messenger RNA in human colon carcinomas and liposarcomas. Cancer Res 46:6169–6173PubMedGoogle Scholar
  35. 35.
    Sjoblom T, Jones S, Wood LD et al (2006) The consensus coding sequence of human breast and colorectal cancers. Science 314:268–274CrossRefPubMedGoogle Scholar
  36. 36.
    Wood LD, Parsons DW, Jones S et al (2007) The genomic landscapes of human breast and colorectal cancers. Science 318:1108–1113CrossRefPubMedGoogle Scholar
  37. 37.
    Advani AS, Hunger SP, Burnett AK (2009) Acute leukemia in adolescents and young adults. Semin Oncol 36:213–226CrossRefPubMedGoogle Scholar
  38. 38.
    Stock W (2010) Adolescents and young adults with acute lymphoblastic leukemia. Hematol Am Soc Hematol Educ Program 2010:21–29Google Scholar
  39. 39.
    Bleyer A, Siegel SE, Coccia PF, Stock W, Seibel NL (2012) Children, adolescents, and young adults with leukemia: the empty half of the glass is growing. J Clin Oncol 30:4037–4038CrossRefPubMedGoogle Scholar
  40. 40.
    Keegan RHM, Reis LAG, Barr RD, Dahike DV, Pollock BH, Bleyer A (2015) Comparison of cancer survival trends in the United States of adolescents and young adults with those in children and older adults. Cancer (in press)Google Scholar
  41. 41.
    Barr R, Ries L, Lewis D, Harlan I, Keegan T, Pollock BH, Bleyer A (2015) Incidence and incidence trends of the most frequent cancers in adolescent and young adult Americans, including “non-malignant” tumors. Cancer (in press)Google Scholar
  42. 42.
    Herold T, Baldus CD, Gokbuget N (2014) Ph like ALL in older adults. N Engl J Med 371:2235CrossRefPubMedGoogle Scholar
  43. 43.
    Roberts KG, Li Y, Payne-Turner D et al (2014) Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. N Engl J Med 371:1005–1015CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Mullighan CG, Zhang J, Harvey RC et al (2009) JAK mutations in high risk childhood acute lymphoblastic leukemia. Proc Natl Acad Sci U S A 106:9414–9418CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Tasian SK, Doral MY, Mullighan CG et al (2012) Aberrant JAK/STAT and PI3K/mTOR pathway signaling occurs in human CRLF2-rearranged B-precursor acute lymphoblastic leukemias. Blood 120:833–842CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Maude SL, Tasian SK, Vincent T et al (2012) Targeting Jak1/2 and mTOR in murine xenograft models of Ph-like acute lymphoblastic leukemia. Blood 120:3510–3518CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Loh ML, Zhang J, Mullighan CG et al (2013) Tyrosine kinome sequencing of high risk pediatric acute lymphoblastic leukemia: a report from The Children’s Oncology Group TARGET Project. Blood 121:485–488CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Perez-Andreu V, Roberts KG, Xu H et al (2015) A genome-wide association study of susceptibility to acute lymphoblastic leukemia in adolescents and young adults. Blood 22:680–686CrossRefGoogle Scholar
  49. 49.
    Kang H, Chen IM, Wilson CS et al (2010) Gene expression classifiers for relapse free survival and minimal residual disease improve risk classification and outcome prediction in pediatric B-precursor acute lymphoblastic leukemia. Blood 115:1394–1405CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2013) GLOBOCAN 2012 v1.0, cancer incidence and mortality worldwide: IARC CancerBase No. 11 [Internet]. International Agency for Research on Cancer, Lyon, Available from: http://globocan.iarc.fr, accessed on 9/14/2015, version 9.13.2015Google Scholar
  51. 51.
    Anders CK, Fan C, Parker JS, Carey LA et al (2011) Breast carcinomas arising at a young age: unique biology or a surrogate for aggressive intrinsic subtypes? J Clin Oncol 29:e18–e20, epubCrossRefPubMedGoogle Scholar
  52. 52.
    Narod SA (2012) Breast cancer in young women. Nat Rev Clin Oncol 9:460–470CrossRefPubMedGoogle Scholar
  53. 53.
    Johnson RH, Chien FL, Bleyer A (2013) Incidence of breast cancer with distant involvement among women in the United States, 1976 to 2009. JAMA 309:800–805CrossRefPubMedGoogle Scholar
  54. 54.
    Jenkins EO, Deal AM, Anders C, Prat A, Perou CM, Carey LA, Muss HB (2014) Age-specific changes in intrinsic breast cancer subtypes. Oncologist 19:1076–1083CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Anders CK, Acharya CR, Hsu DS et al (2008) Age-specific differences in oncogenic pathway deregulation seen in human breast tumors. PLoS One 3(1):e1373CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Anders CK, Hsu DS, Broadwater G et al (2008) Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression. J Clin Oncol 26:3324–3330CrossRefPubMedGoogle Scholar
  57. 57.
    Azim HA Jr, Michiels S, Bedard PL et al (2012) Elucidating prognosis and biology of breast cancer arising in young women using gene expression profiling. Clin Cancer Res 18:1341–1351CrossRefPubMedGoogle Scholar
  58. 58.
    Carvalho LV, Pereira EM, Frappart L et al (1992) Molecular characterization of breast cancer in young Brazilian women. Rev Assoc Med Bras 56:278–287Google Scholar
  59. 59.
    Collins LC, Marotti JD, Gelber S et al (2012) Pathologic features and molecular phenotype by patient age in a large cohort of young women with breast cancer. Breast Cancer Res Treat 131:1061–1066CrossRefPubMedGoogle Scholar
  60. 60.
    Young SR, Pilarski RT, Donenberg T et al (2009) The prevalence of BRCA1 mutations among young women with triple-negative breast cancer. BMC Cancer 9:86, epubCrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Zhang Q, Zhang Q, Cong H, Zhang X (2012) The ectopic expression of BRCA1 is associated with genesis, progression, and prognosis of breast cancer in young patients. Diagn Pathol 7:181, epubCrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Guttery DS, Hancox RA, Mulligan KT et al (2010) Association of invasion-promoting tenascin-C additional domains with breast cancers in young women. Breast Cancer Res 12:R57, epubCrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    TCGA: The Cancer Genome Atlas Network (2012) Comprehensive molecular portraits of human breast tumours. Nature 490:61–70CrossRefPubMedCentralGoogle Scholar
  64. 64.
    Prat A, Adamo B, Cheang MC et al (2013) Molecular characterization of basal-like and non-basal-like triple-negative breast cancer. Oncologist 18:123–133CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Servant N, Bollet MA, Halfwerk H et al (2012) Search for a gene expression signature of breast cancer local recurrence in young women. Clin Cancer Res 18:1704–1715CrossRefPubMedGoogle Scholar
  66. 66.
    Loo LW, Wang Y, Flynn EM et al (2011) Genome-wide copy number alterations in subtypes of invasive breast cancers in young white and African American women. Breast Cancer Res Treat 127:297–308CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Stevens KN, Vachon CM, Lee AM et al (2011) Common breast cancer susceptibility loci are associated with triple-negative breast cancer. Cancer Res 71:6240–6249CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Lange JR, Palis BE, Chang DC et al (2007) Melanoma in children and teenagers: an analysis of patients from the National Cancer Data Base. J Clin Oncol 25:1363–1368CrossRefPubMedGoogle Scholar
  69. 69.
    Dadras SS (2011) Molecular diagnostics in melanoma: current status and perspectives. Arch Pathol Lab Med 135:860–869PubMedGoogle Scholar
  70. 70.
    Bastian BC, Wesselmann U, Pinkel D, Leboit PE (1999) Molecular cytogenetic analysis of Spitz nevi shows clear differences to melanoma. J Invest Dermatol 113:1065–1069CrossRefPubMedGoogle Scholar
  71. 71.
    Uribe P, Wistuba II, Solar A et al (2005) Comparative analysis of loss of heterozygosity and microsatellite instability in adult and pediatric melanoma. Am J Dermatopathol 27:279–285CrossRefPubMedGoogle Scholar
  72. 72.
    Hansson J (2008) Familial melanoma. Surg Clin North Am 88:897–916CrossRefPubMedGoogle Scholar
  73. 73.
    van Dijk MC, Bernsen MR, Ruiter DJ (2005) Analysis of mutations in B-RAF, N-RAS, and H-RAS genes in the differential diagnosis of Spitz nevus and spitzoid melanoma. Am J Surg Pathol 29:1145–1151CrossRefPubMedGoogle Scholar
  74. 74.
    Fullen DR, Poynter JN, Lowe L et al (2006) BRAF and NRAS mutations in spitzoid melanocytic lesions. Mod Pathol 19:1324–1332CrossRefPubMedGoogle Scholar
  75. 75.
    Daniotti M, Ferrari A, Frigerio S et al (2009) Cutaneous melanoma in childhood and adolescence shows frequent loss of INK4A and gain of KIT. J Invest Dermatol 129:1759–1768CrossRefPubMedGoogle Scholar
  76. 76.
    Al Dhaybi R, Agoumi M, Gagne I et al (2011) p16 expression: a marker of differentiation between childhood malignant melanomas and Spitz nevi. J Am Acad Dermatol 65:357–363CrossRefPubMedGoogle Scholar
  77. 77.
    Jukic DM, Rao UN, Kelly L et al (2010) Micro RNA profiling analysis of differences between the melanoma of young adults and older adults. J Transl Med 8:27, epubCrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Fletcher CDM et al (eds) (2013) WHO classification of tumours of soft tissue and bone, 4th edn. IARC Press, LyonGoogle Scholar
  79. 79.
    Wagner AJ, Goldberg JM, Dubois SG et al (2012) Tivantinib ARQ 197, a selective inhibitor of MET, in patients with microphthalmia transcription factor-associated tumors. Cancer 118:5894–5902CrossRefPubMedGoogle Scholar
  80. 80.
    Rosenberg AE, Cleton-Jansen AM, de Pineux G et al (2013) Conventional osteosarcoma. In: Fletcher Ch DM, Bridge JA, Hogendoorn PAW (eds) WHO classification of tumours of soft tissue and bone. IARC, LyonGoogle Scholar
  81. 81.
    Mirabello L, Troisi RJ, Savage SA (2009) Osteosarcoma incidence and survival rates from 1973 to 2004: data from the Surveillance, Epidemiology, and End Results Program. Cancer 115:1531–1543CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Stiller CA, Bielack SS, Jundt G, Steliarova-Foucher D (2006) Bone tumours in European children and adolescents, 1978–1997. Report from the Automated Childhood Cancer Information System project. Eur J Cancer 42:2124–2135CrossRefPubMedGoogle Scholar
  83. 83.
    Kansara M, Teng MW, Smyth MJ, Thomas DM (2014) Translational biology of osteosarcoma. Nat Rev Cancer 14:722–735CrossRefPubMedGoogle Scholar
  84. 84.
    Kuijjer ML, Hogendoorn PC, Cleton-Jansen AM (2013) Genome-wide analyses on high-grade osteosarcoma: making sense of a genomically most unstable tumor. Int J Cancer 133:2512–2521PubMedGoogle Scholar
  85. 85.
    Chen X, Armita Bahrami A, Pappo A et al (2014) Recurrent somatic structural variations contribute to tumorigenesis in pediatric osteosarcoma. Cell Rep 7:104–112CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Alexandrov LB, Nik-Zainal S, Wedge DC et al (2013) Signatures of mutational processes in human cancer. Nature 502:415–421CrossRefGoogle Scholar
  87. 87.
    Bielack S, Smeland S, Whelan J et al (2015) Methotrexate, doxorubicin, and cisplatin (map) plus maintenance pegylated interferon alfa-2b versus MAP alone in patients with resectable high-grade osteosarcoma and good histologic response to preoperative MAP: first results of the EURAMOS-1 good response randomized controlled trial. J Clin Oncol 33:2279–2287CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Meyers PA, Schwartz CL, Krailo MD et al (2008) Osteosarcoma: the addition of muramyl tripeptide to chemotherapy improves overall survival – a report from the Children’s Oncology Group. J Clin Oncol 26:633–638CrossRefPubMedGoogle Scholar
  89. 89.
    Antonescu C (2014) Round cell sarcomas beyond Ewing: emerging entities. Histopathlogy 64:26–37CrossRefGoogle Scholar
  90. 90.
    Karski EE, Matthay KK, Neuhaus JM, Goldsby RE, Dubois SG (2013) Characteristics and outcomes of patients with Ewing sarcoma over 40 years of age at diagnosis. Cancer Epidemiol 37:29–33CrossRefPubMedGoogle Scholar
  91. 91.
    Szuhai K, Cleton-Jansen AM, Hogendoorn PA et al (2012) Cancer Genet 205:193–204CrossRefPubMedGoogle Scholar
  92. 92.
    de Alava E, Lessnick SL, Sorensen PH (2013) Ewing sarcoma. In: Fletcher Ch DM, Bridge JA, Hogendoorn PAW (eds) WHO classification of tumours of soft tissue and bone. IARC, LyonGoogle Scholar
  93. 93.
    Toomey EC, Schiffman JD, Lessnick SL (2010) Recent advances in the molecular pathogenesis of Ewing’s sarcoma. Oncogene 29:4504–4516CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Lessnick SL, Ladanyi M (2012) Molecular pathogenesis of Ewing sarcoma: new therapeutic and transcriptional targets. Annu Rev Pathol 7:145–159CrossRefPubMedGoogle Scholar
  95. 95.
    Schwartz JC, Cech TR, Parker RR (2015) Biochemical properties and biological functions of FET proteins. Ann Rev Biochem 84:355–379CrossRefPubMedGoogle Scholar
  96. 96.
    Kar A, Gutierrez-Hartmann A (2013) Molecular mechanisms of ETS transcription factor-mediated tumorigenesis. Crit Rev Biochem Mol Biol 48:522–543CrossRefPubMedPubMedCentralGoogle Scholar
  97. 97.
    Kovar H (2010) Downstream EWS/FLI1 – upstream Ewing’s sarcoma. Genome Med 2:8CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Sand LG, Szuhai K, Hogendoorn PCW (2015) Sequencing overview of Ewing sarcoma: a journey across genomic, epigenomic and transcriptomic landscapes. Int J Mol Sci 16:1617–6215Google Scholar
  99. 99.
    Mackintosh C, Madoz-Gurpide J, Ordonez JL et al (2010) The molecular pathogenesis of Ewing’s sarcoma. Cancer Biol Ther 9:655–667CrossRefPubMedGoogle Scholar
  100. 100.
    Riggi N, Knoechel B, Gillespie SM et al (2014) EWS-FLI1 utilizes divergent chromatin remodeling mechanisms to directly activate or repress enhancer elements in Ewing sarcoma. Cancer Cell 28:668–681CrossRefGoogle Scholar
  101. 101.
    Tomazou EM, Sheffield NC, Schmidt C et al (2015) Epigenome mapping reveals distinct modes of gene regulation and widespread enhancer reprogramming by the oncogenic fusion protein EWS-FLI1. Cell Rep 10:1082–1095CrossRefPubMedPubMedCentralGoogle Scholar
  102. 102.
    Tsuda M, Davis IJ, Argani P et al (2007) TFE3 fusions activate MET signaling by transcriptional up-regulation, defining another class of tumors as candidates for therapeutic MET inhibition. Cancer Res 67:919–929CrossRefPubMedGoogle Scholar
  103. 103.
    Taylor JGT, Cheuk AT, Tsang PS et al (2009) Identification of FGFR4-activating mutations in human rhabdomyosarcomas that promote metastasis in xenotransplanted models. J Clin Invest 119:3395–3407PubMedGoogle Scholar
  104. 104.
    Cao L, Yu Y, Bilke S et al (2010) Genome-wide identification of PAX3-FKHR binding sites in rhabdomyosarcoma reveals candidate target genes important for development and cancer. Cancer Res 70:6497–6508CrossRefPubMedPubMedCentralGoogle Scholar
  105. 105.
    Taulli R, Scuoppo C, Bersani F et al (2006) Validation of met as a therapeutic target in alveolar and embryonal rhabdomyosarcoma. Cancer Res 66:4742–4749CrossRefPubMedGoogle Scholar
  106. 106.
    Grohar PJ, Woldemichael GM, Griffin LB et al (2011) Identification of an inhibitor of the EWS-FLI1 oncogenic transcription factor by high-throughput screening. J Natl Cancer Inst 103:962–978CrossRefPubMedPubMedCentralGoogle Scholar
  107. 107.
    Dagher R, Long LM, Read EJ et al (2002) Pilot trial of tumor-specific peptide vaccination and continuous infusion interleukin-2 in patients with recurrent Ewing sarcoma and alveolar rhabdomyosarcoma: an inter-institute NIH study. Med Pediatr Oncol 38:158–164CrossRefPubMedGoogle Scholar
  108. 108.
    Le Deley MC, Delattre O, Schaefer KL et al (2010) Impact of EWS-ETS fusion type on disease progression in Ewing’s sarcoma/peripheral primitive neuroectodermal tumor: prospective results from the cooperative Euro-E.W.I.N.G. 99 trial. J Clin Oncol 28:1982–1988CrossRefPubMedGoogle Scholar
  109. 109.
    van Doorninck JA, Ji L, Schaub B, Shimada H et al (2010) Current treatment protocols have eliminated the prognostic advantage of type 1 fusions in Ewing sarcoma: a report from the Children’s Oncology Group. J Clin Oncol 28:1989–1994CrossRefPubMedPubMedCentralGoogle Scholar
  110. 110.
    Kovar H (2014) Blocking the road, stopping the engine or killing the driver? Advances in targeting EWS/FLI-1 fusion in Ewing sarcoma as novel therapy. Expert Opin Ther Targets 18:1315–1328CrossRefPubMedGoogle Scholar
  111. 111.
    Potratz J, Heribert Jürgens H, Craft A, Dirksen U (2012) Ewing sarcoma: biology-based therapeutic perspectives. Pediatr Hematol Oncol 29:12–27CrossRefPubMedGoogle Scholar
  112. 112.
    Stuurmeijer AJ, de Bruin D, Kessel A et al (2013) Synovial sarcoma. In: Fletcher CDM, Bridge JA, Hogendoorn PAW (eds) WHO classification of tumours of soft tissue and bone. IARC, Lyon, pp 213–215Google Scholar
  113. 113.
    Sultan I, Rodriguez-Galindo C, Saab R et al (2009) Comparing children and adults with synovial sarcoma in the Surveillance, Epidemiology, and End Results program, 1983 to 2005: an analysis of 1268 patients. Cancer 115:3537–3547CrossRefPubMedGoogle Scholar
  114. 114.
    Vienterie M, Ho V, Kaal SEJ et al (2015) Age as an independent prognostic factor for survival of localised synovial sarcoma patients. Br J Cancer 113:1602–1606CrossRefGoogle Scholar
  115. 115.
    Thway K, Fisher C (2014) Synovial sarcoma: defining features and diagnostic evolution. Ann Diagn Pathol 18:369–380CrossRefPubMedGoogle Scholar
  116. 116.
    Kerouanton A, Jimenez I, Cellier C et al (2014) Synovial sarcoma in children and adolescents. J Pediatr Hematol Oncol 36:257–262CrossRefPubMedGoogle Scholar
  117. 117.
    Kubo T, Shimose S, Fujimori J et al (2015) Prognostic value of SS18-SSX fusion type in synovial sarcoma; systematic review and meta-analysis. SpringerPlus 4:375CrossRefPubMedPubMedCentralGoogle Scholar
  118. 118.
    Nielsen TO, Poulin NM, Ladanyi M (2015) Synovial sarcoma: recent discoveries as a roadmap to new avenues for therapy. Cancer Discov 5:124–134CrossRefPubMedPubMedCentralGoogle Scholar
  119. 119.
    Kadoch C, Crabtree GR (2013) Reversible disruption of mSWI/SNF (BAF) complexes by the SS18-SSX oncogenic fusion in synovial sarcoma. Cell 153:71–85CrossRefPubMedPubMedCentralGoogle Scholar
  120. 120.
    Su L, Sampaio AV, Jones KB et al (2012) Deconstruction of the SS18-SSX fusion oncoprotein complex: insights into disease etiology and therapeutics. Cancer Cell 21:333–347CrossRefPubMedPubMedCentralGoogle Scholar
  121. 121.
    Vienterie M, Hillebrandt-Roeffen MHS, Flucke U et al (2015) Next generation sequencing in synovial sarcoma reveals novel gene mutations. Oncotarget 34:680–690Google Scholar
  122. 122.
    Lagarde P, Przybyl J, Brulard C et al (2013) Chromosome instability accounts for reverse metastatic outcomes of pediatric and adult synovial sarcomas. J Clin Oncol 31:608–615CrossRefPubMedGoogle Scholar
  123. 123.
    Przybyl J, Sciot R, Wozniak A et al (2014) Metastatic potential is determined early in synovial sarcoma development and reflected by tumor molecular features. Int J Biochem Cell Biol 53:505–513CrossRefPubMedGoogle Scholar
  124. 124.
    Joseph CG, Hwang H, Jiao Y et al (2014) Exomic analysis of myxoid liposarcomas, synovial sarcomas, and osteosarcomas. Gene Chromosome Cancer 53:15–24CrossRefGoogle Scholar
  125. 125.
    Ferrari A, Rognone A, Casanova M et al (2008) Colon carcinoma in children and adolescents: the experience of the Istituto Nazionale Tumori of Milan, Italy. Pediatr Blood Cancer 50:588–593CrossRefPubMedGoogle Scholar
  126. 126.
    Hubbard JM, Grothey A (2013) Adolescent and young adult colon cancer. J Natl Compr Cancer Netw 11:1219–1225CrossRefGoogle Scholar

Copyright information

© Springer International Publishing 2017

Authors and Affiliations

  • James V. Tricoli
    • 1
  • Archie Bleyer
    • 2
  • Jakob Anninga
    • 3
  • Ronald Barr
    • 4
  1. 1.Diagnostic Biomarkers and Technology Branch, Division of Cancer Treatment and DiagnosisNational Cancer Institute, NIHBethesdaUSA
  2. 2.Department of Radiation MedicineOregon Health and Sciences UniversityBendUSA
  3. 3.Department of Clinical OncologyLeiden University Medical CentreLeidenThe Netherlands
  4. 4.Departments of Pediatrics, Pathology and MedicineMcMaster UniversityHamiltonCanada

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