Skip to main content
SpringerLink
Log in

Epidemiology, Biology, and Genetics of Adult Male Germ Cell Tumors

  • Chapter
  • First Online:
Urological Oncology

  • 1632 Accesses

Abstract

While germ cell tumors (GCTs) comprise only about 1 % of cancers diagnosed each year in American men, they still constitute the most common malignancy to affect male adolescent and young adults (AYA) in the US and other developed countries. Most commonly, these tumors originate in the testis and comprise more than 95 % of all testicular malignancies. However, GCTs can also arise in extragonadal locations such as the mediastinum, pineal gland, and retroperitoneum. Despite having a nearly universal genetic marker, isochromosome 12p, GCTs are not a singular tumor type but rather a fascinating group of malignancies derived from the malignant transformation of developing germ cells. The pluripotential differentiating capacity of developing germ cells explains the intriguing biology and array of histologies found in GCTs. These histologies mimic the cell and tissue types seen during embryologic and extraembryologic fetal development. In this chapter, the authors review GCT epidemiology, highlighting well-known risk factors such as cryptorchidism as well as newly appreciated risk factors such as infertility and genetic polymorphisms, with plausible explanations of how these characteristics may be interrelated. An overview of the biology of GCT development and differentiation is also presented with an emphasis on recent insights and persistent controversies. The authors provide a detailed review of GCT genetics including potential candidate genes and regions within 12p and other frequent chromosomal aberrations. In the latter part of the chapter, the authors summarize the data supporting and refuting proposed explanations for the exquisite sensitivity of most GCTs to cisplatin, which underlies their unique curability even in the setting of widely metastatic disease. Finally, various mechanisms by which GCTs might acquire or have inherent cisplatin resistance are presented. As such, the reader of this chapter will be left with a solid understanding of the epidemiology, biology, and genetics of this fascinating malignancy.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Biggs ML, Schwartz SM. Cancer of the testis. In: Ries LAG et al., editors. SEER survival monograph: cancer survival among adults: U.S. SEER program, 1988–2001, patient and tumor characteristics. Bethesda: National Cancer Institute; 2007. p. 165–70.

    Google Scholar 

  2. Feldman DR, et al. Medical treatment of advanced testicular cancer. JAMA. 2008;299(6): 672–84.

    Google Scholar 

  3. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62(1):10–29.

    PubMed  Google Scholar 

  4. Risk MC, Porter CR. Management of non-germinal testicular tumors. World J Urol. 2009;27(4):507–12.

    PubMed  Google Scholar 

  5. Stang A, et al. Gonadal and extragonadal germ cell tumours in the United States, 1973–2007. Int J Androl. 2012;35(4):616–25.

    CAS  PubMed Central  PubMed  Google Scholar 

  6. Chia VM, et al. International trends in the incidence of testicular cancer, 1973–2002. Cancer Epidemiol Biomarkers Prev. 2010;19(5):1151–9.

    PubMed Central  PubMed  Google Scholar 

  7. Howlader N, et al. SEER cancer statistics review, 1975–2008. 2011 [cited 2012; Available from: http://seer.cancer.gov/csr/1975_2008/. Last Accessed on Apr 15th 2014.

  8. McGlynn KA, et al. Trends in the incidence of testicular germ cell tumors in the United States. Cancer. 2003;97(1):63–70.

    PubMed  Google Scholar 

  9. Townsend JS, Richardson LC, German RR. Incidence of testicular cancer in the United States, 1999–2004. Am J Mens Health. 2010;4(4):353–60.

    PubMed  Google Scholar 

  10. Wood HM, Elder JS. Cryptorchidism and testicular cancer: separating fact from fiction. J Urol. 2009;181(2):452–61.

    PubMed  Google Scholar 

  11. Myrup C, Schnack TH, Wohlfahrt J. Correction of cryptorchidism and testicular cancer. N Engl J Med. 2007;357(8):825–7; author reply 825–7.

    CAS  PubMed  Google Scholar 

  12. Schnack TH, et al. Familial coaggregation of cryptorchidism, hypospadias, and testicular germ cell cancer: a nationwide cohort study. J Natl Cancer Inst. 2010;102(3):187–92.

    CAS  PubMed  Google Scholar 

  13. Raman JD, Nobert CF, Goldstein M. Increased incidence of testicular cancer in men presenting with infertility and abnormal semen analysis. J Urol. 2005;174(5):1819–22; discussion 1822.

    PubMed  Google Scholar 

  14. Cools M, et al. Germ cell tumors in the intersex gonad: old paths, new directions, moving frontiers. Endocr Rev. 2006;27(5):468–84.

    CAS  PubMed  Google Scholar 

  15. Fossa SD, et al. Risk of contralateral testicular cancer: a population-based study of 29,515 U.S. men. J Natl Cancer Inst. 2005;97(14):1056–66.

    PubMed  Google Scholar 

  16. Andreassen KE, et al. Risk of metachronous contralateral testicular germ cell tumors: a population-based study of 7,102 Norwegian patients (1953–2007). Int J Cancer. 2011;129(12):2867–74.

    CAS  PubMed  Google Scholar 

  17. Osterlind A, et al. Incidence of bilateral testicular germ cell cancer in Denmark, 1960–84: preliminary findings. Int J Androl. 1987;10(1):203–8.

    CAS  PubMed  Google Scholar 

  18. Skakkebaek NE. Possible carcinoma-in-situ of the testis. Lancet. 1972;2(7776):516–7.

    CAS  PubMed  Google Scholar 

  19. von der Maase H, et al. Carcinoma in situ of contralateral testis in patients with testicular germ cell cancer: study of 27 cases in 500 patients. Br Med J (Clin Res Ed). 1986;293(6559):1398–401.

    Google Scholar 

  20. Hartmann JT, et al. The relative risk of second nongerminal malignancies in patients with extragonadal germ cell tumors. Cancer. 2000;88(11):2629–35.

    CAS  PubMed  Google Scholar 

  21. Heimdal K, et al. Familial testicular cancer in Norway and Southern Sweden. Br J Cancer. 1996;73(7):964–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  22. Sonneveld DJ, et al. Familial testicular cancer in a single-centre population. Eur J Cancer. 1999;35(9):1368–73.

    CAS  PubMed  Google Scholar 

  23. Spermon JR, et al. Cancer incidence in relatives of patients with testicular cancer in the eastern part of The Netherlands. Urology. 2001;57(4):747–52.

    CAS  PubMed  Google Scholar 

  24. Westergaard T, et al. Cancer risk in fathers and brothers of testicular cancer patients in Denmark. A population-based study. Int J Cancer. 1996;66(5):627–31.

    CAS  PubMed  Google Scholar 

  25. Kanetsky PA, et al. Common variation in KITLG and at 5q31.3 predisposes to testicular germ cell cancer. Nat Genet. 2009;41(7):811–5.

    CAS  PubMed Central  PubMed  Google Scholar 

  26. Rapley EA, et al. Somatic mutations of KIT in familial testicular germ cell tumours. Br J Cancer. 2004;90(12):2397–401.

    CAS  PubMed Central  PubMed  Google Scholar 

  27. Blume-Jensen P, et al. Kit/stem cell factor receptor-induced activation of phosphatidylinositol 3’-kinase is essential for male fertility. Nat Genet. 2000;24(2):157–62.

    CAS  PubMed  Google Scholar 

  28. Gu Y, et al. Steel factor controls primordial germ cell survival and motility from the time of their specification in the allantois, and provides a continuous niche throughout their migration. Development. 2009;136(8):1295–303.

    CAS  PubMed  Google Scholar 

  29. Daling JR, et al. Association of marijuana use and the incidence of testicular germ cell tumors. Cancer. 2009;115(6):1215–23.

    PubMed Central  PubMed  Google Scholar 

  30. Trabert B, et al. Marijuana use and testicular germ cell tumors. Cancer. 2011;117(4):848–53.

    PubMed Central  PubMed  Google Scholar 

  31. Hardell L, et al. Increased concentrations of polychlorinated biphenyls, hexachlorobenzene, and chlordanes in mothers of men with testicular cancer. Environ Health Perspect. 2003;111(7):930–4.

    CAS  PubMed Central  PubMed  Google Scholar 

  32. McGlynn KA, et al. Persistent organochlorine pesticides and risk of testicular germ cell tumors. J Natl Cancer Inst. 2008;100(9):663–71.

    CAS  PubMed  Google Scholar 

  33. Nichols CR, et al. Klinefelter’s syndrome associated with mediastinal germ cell neoplasms. J Clin Oncol. 1987;5(8):1290–4.

    CAS  PubMed  Google Scholar 

  34. Ginsburg M, Snow MH, McLaren A. Primordial germ cells in the mouse embryo during gastrulation. Development. 1990;110(2):521–8.

    CAS  PubMed  Google Scholar 

  35. Skakkebaek NE. Carcinoma in situ of the testis: frequency and relationship to invasive germ cell tumours in infertile men. Histopathology. 1978;2(3):157–70.

    CAS  PubMed  Google Scholar 

  36. de Jong J, et al. Diagnostic value of OCT3/4 for pre-invasive and invasive testicular germ cell tumours. J Pathol. 2005;206(2):242–9.

    PubMed  Google Scholar 

  37. Jones TD, et al. OCT4 staining in testicular tumors: a sensitive and specific marker for seminoma and embryonal carcinoma. Am J Surg Pathol. 2004;28(7):935–40.

    PubMed  Google Scholar 

  38. Koshida K, Uchibayashi T, Hisazumi H. Characterization of seminoma-derived placental-like alkaline phosphatase. Urol Int. 1991;47 Suppl 1:96–9.

    PubMed  Google Scholar 

  39. Donovan PJ, de Miguel MP. Turning germ cells into stem cells. Curr Opin Genet Dev. 2003;13(5):463–71.

    CAS  PubMed  Google Scholar 

  40. Durcova-Hills G, et al. Reprogramming primordial germ cells into pluripotent stem cells. PLoS One. 2008;3(10):e3531.

    PubMed Central  PubMed  Google Scholar 

  41. Looijenga LH, Stoop H, de Leeuw HP, et al. POU5F1 (OCT3/4) identifies cells with pluripotent potential in human germ cell tumors.Cancer Res 2003;63(9):2244–2250.

    Google Scholar 

  42. Sperger JM, et al. Gene expression patterns in human embryonic stem cells and human pluripotent germ cell tumors. Proc Natl Acad Sci U S A. 2003;100(23):13350–5.

    CAS  PubMed Central  PubMed  Google Scholar 

  43. Brivanlou AH, et al. Stem cells. Setting standards for human embryonic stem cells. Science. 2003;300(5621):913–6.

    CAS  PubMed  Google Scholar 

  44. Korkola JE, et al. Down-regulation of stem cell genes, including those in a 200-kb gene cluster at 12p13.31, is associated with in vivo differentiation of human male germ cell tumors. Cancer Res. 2006;66(2):820–7.

    CAS  PubMed  Google Scholar 

  45. Samaniego F, et al. Cytogenetic and molecular analysis of human male germ cell tumors: chromosome 12 abnormalities and gene amplification. Genes Chromosomes Cancer. 1990;1(4):289–300.

    CAS  PubMed  Google Scholar 

  46. Skakkebaek NE, et al. Carcinoma-in-situ of the testis: possible origin from gonocytes and precursor of all types of germ cell tumours except spermatocytoma. Int J Androl. 1987;10(1):19–28.

    CAS  PubMed  Google Scholar 

  47. Ottesen AM, et al. High-resolution comparative genomic hybridization detects extra chromosome arm 12p material in most cases of carcinoma in situ adjacent to overt germ cell tumors, but not before the invasive tumor development. Genes Chromosomes Cancer. 2003;38(2):117–25.

    CAS  PubMed  Google Scholar 

  48. Summersgill B, et al. Chromosomal imbalances associated with carcinoma in situ and associated testicular germ cell tumours of adolescents and adults. Br J Cancer. 2001;85(2):213–20.

    CAS  PubMed Central  PubMed  Google Scholar 

  49. Chaganti RS, Houldsworth J. The cytogenetic theory of the pathogenesis of human adult male germ cell tumors. Review article APMIS. 1998;106(1):80–3; discussion 83–4.

    CAS  Google Scholar 

  50. Angulo JC, et al. Clinicopathological study of regressed testicular tumors (apparent extragonadal germ cell neoplasms). J Urol. 2009;182(5):2303–10.

    PubMed  Google Scholar 

  51. Balzer BL, Ulbright TM. Spontaneous regression of testicular germ cell tumors: an analysis of 42 cases. Am J Surg Pathol. 2006;30(7):858–65.

    PubMed  Google Scholar 

  52. Chaganti RS, Houldsworth J. Genetics and biology of adult human male germ cell tumors. Cancer Res. 2000;60(6):1475–82.

    CAS  PubMed  Google Scholar 

  53. Atkin NB, Baker MC. Specific chromosome change, i(12p), in testicular tumours? Lancet. 1982;2(8311):1349.

    CAS  PubMed  Google Scholar 

  54. Rodriguez E, et al. Molecular cytogenetic analysis of i(12p)-negative human male germ cell tumors. Genes Chromosomes Cancer. 1993;8(4):230–6.

    CAS  PubMed  Google Scholar 

  55. Motzer RJ, et al. Molecular and cytogenetic studies in the diagnosis of patients with poorly differentiated carcinomas of unknown primary site. J Clin Oncol. 1995;13(1):274–82.

    CAS  PubMed  Google Scholar 

  56. Rosenberg C, et al. Overrepresentation of the short arm of chromosome 12 is related to invasive growth of human testicular seminomas and nonseminomas. Oncogene. 2000;19(51):5858–62.

    CAS  PubMed  Google Scholar 

  57. Vos A, et al. Cytogenetics of carcinoma in situ of the testis. Cancer Genet Cytogenet. 1990;46(1):75–81.

    CAS  PubMed  Google Scholar 

  58. Houldsworth J, et al. Aberrant expression of cyclin D2 is an early event in human male germ cell tumorigenesis. Cell Growth Differ. 1997;8(3):293–9.

    CAS  PubMed  Google Scholar 

  59. Clark AT, et al. Human STELLAR, NANOG, and GDF3 genes are expressed in pluripotent cells and map to chromosome 12p13, a hotspot for teratocarcinoma. Stem Cells. 2004;22(2):169–79.

    CAS  PubMed  Google Scholar 

  60. Giuliano CJ, et al. Retinoic acid represses a cassette of candidate pluripotency chromosome 12p genes during induced loss of human embryonal carcinoma tumorigenicity. Biochim Biophys Acta. 2005;1731(1):48–56.

    CAS  PubMed  Google Scholar 

  61. Mostert MM, et al. Comparative genomic hybridization of germ cell tumors of the adult testis: confirmation of karyotypic findings and identification of a 12p-amplicon. Cancer Genet Cytogenet. 1996;89(2):146–52.

    CAS  PubMed  Google Scholar 

  62. Rao PH, et al. Chromosomal amplification is associated with cisplatin resistance of human male germ cell tumors. Cancer Res. 1998;58(19):4260–3.

    CAS  PubMed  Google Scholar 

  63. Bourdon V, et al. Genomic and expression analysis of the 12p11-p12 amplicon using EST arrays identifies two novel amplified and overexpressed genes. Cancer Res. 2002;62(21):6218–23.

    CAS  PubMed  Google Scholar 

  64. Rodriguez S, et al. Expression profile of genes from 12p in testicular germ cell tumors of adolescents and adults associated with i(12p) and amplification at 12p11.2-p12.1. Oncogene. 2003;22(12):1880–91.

    CAS  PubMed  Google Scholar 

  65. Zafarana G, et al. 12p-amplicon structure analysis in testicular germ cell tumors of adolescents and adults by array CGH. Oncogene. 2003;22(48):7695–701.

    CAS  PubMed  Google Scholar 

  66. Murty VV, Chaganti RS. A genetic perspective of male germ cell tumors. Semin Oncol. 1998;25(2):133–44.

    CAS  PubMed  Google Scholar 

  67. Rodriguez E, et al. Cytogenetic analysis of 124 prospectively ascertained male germ cell tumors. Cancer Res. 1992;52(8):2285–91.

    CAS  PubMed  Google Scholar 

  68. Murty VV, et al. Allelic loss and somatic differentiation in human male germ cell tumors. Oncogene. 1994;9(8):2245–51.

    CAS  PubMed  Google Scholar 

  69. Mathew S, et al. Loss of heterozygosity identifies multiple sites of allelic deletions on chromosome 1 in human male germ cell tumors. Cancer Res. 1994;54(23):6265–9.

    CAS  PubMed  Google Scholar 

  70. Koul S, et al. Characteristic promoter hypermethylation signatures in male germ cell tumors. Mol Cancer. 2002;1:8.

    PubMed Central  PubMed  Google Scholar 

  71. Smith-Sorensen B, et al. Frequent promoter hypermethylation of the O6-Methylguanine-DNA Methyltransferase (MGMT) gene in testicular cancer. Oncogene. 2002;21(57):8878–84.

    CAS  PubMed  Google Scholar 

  72. Honorio S, et al. Frequent epigenetic inactivation of the RASSF1A tumour suppressor gene in testicular tumours and distinct methylation profiles of seminoma and nonseminoma testicular germ cell tumours. Oncogene. 2003;22(3):461–6.

    CAS  PubMed  Google Scholar 

  73. Roelofs H, et al. Restricted 12p amplification and RAS mutation in human germ cell tumors of the adult testis. Am J Pathol. 2000;157(4):1155–66.

    CAS  PubMed Central  PubMed  Google Scholar 

  74. Looijenga LH, et al. Stem cell factor receptor (c-KIT) codon 816 mutations predict development of bilateral testicular germ-cell tumors. Cancer Res. 2003;63(22):7674–8.

    CAS  PubMed  Google Scholar 

  75. Tian Q, et al. Activating c-kit gene mutations in human germ cell tumors. Am J Pathol. 1999;154(6):1643–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  76. Bouras M, et al. A novel SMAD4 gene mutation in seminoma germ cell tumors. Cancer Res. 2000;60(4):922–8.

    CAS  PubMed  Google Scholar 

  77. Coffey J, et al. Somatic KIT mutations occur predominantly in seminoma germ cell tumors and are not predictive of bilateral disease: report of 220 tumors and review of literature. Genes Chromosomes Cancer. 2008;47(1):34–42.

    CAS  PubMed  Google Scholar 

  78. Sakuma Y, et al. Mutations of c-kit gene in bilateral testicular germ cell tumours in Japan. Cancer Lett. 2008;259(1):119–26.

    CAS  PubMed  Google Scholar 

  79. Einhorn LH, Donohue J. Cis-diamminedichloroplatinum, vinblastine, and bleomycin combination chemotherapy in disseminated testicular cancer. Ann Intern Med. 1977;87(3):293–8.

    CAS  PubMed  Google Scholar 

  80. Grobholz R, et al. Bax, Bcl-2, fas and Fas-L antigen expression in human seminoma: correlation with the apoptotic index. APMIS. 2002;110(10):724–32.

    CAS  PubMed  Google Scholar 

  81. Mayer F, et al. Molecular determinants of treatment response in human germ cell tumors. Clin Cancer Res. 2003;9(2):767–73.

    CAS  PubMed  Google Scholar 

  82. Soini Y, Paakko P. Extent of apoptosis in relation to p53 and bcl-2 expression in germ cell tumors. Hum Pathol. 1996;27(11):1221–6.

    CAS  PubMed  Google Scholar 

  83. Mazumdar M, et al. Cluster analysis of p53 and Ki67 expression, apoptosis, alpha-fetoprotein, and human chorionic gonadotrophin indicates a favorable prognostic subgroup within the embryonal carcinoma germ cell tumor. J Clin Oncol. 2003;21(14):2679–88.

    CAS  PubMed  Google Scholar 

  84. Logothetis CJ, et al. The growing teratoma syndrome. Cancer. 1982;50(8):1629–35.

    CAS  PubMed  Google Scholar 

  85. Donadio AC, et al. Chemotherapy for teratoma with malignant transformation. J Clin Oncol. 2003;21(23):4285–91.

    CAS  PubMed  Google Scholar 

  86. Timmer-Bosscha H, et al. Differential effects of all-trans-retinoic acid, docosahexaenoic acid, and hexadecylphosphocholine on cisplatin-induced cytotoxicity and apoptosis in a cisplantin-sensitive and resistant human embryonal carcinoma cell line. Cancer Chemother Pharmacol. 1998;41(6):469–76.

    CAS  PubMed  Google Scholar 

  87. Mueller T, et al. Loss of Oct-3/4 expression in embryonal carcinoma cells is associated with induction of cisplatin resistance. Tumour Biol. 2006;27(2):71–83.

    CAS  PubMed  Google Scholar 

  88. Zamble DB, et al. Testis-specific HMG-domain protein alters the responses of cells to cisplatin. J Inorg Biochem. 2002;91(3):451–62.

    CAS  PubMed  Google Scholar 

  89. Welsh C, et al. Reduced levels of XPA, ERCC1 and XPF DNA repair proteins in testis tumor cell lines. Int J Cancer. 2004;110(3):352–61.

    CAS  PubMed  Google Scholar 

  90. Koberle B, et al. Defective repair of cisplatin-induced DNA damage caused by reduced XPA protein in testicular germ cell tumours. Curr Biol. 1999;9(5):273–6.

    CAS  PubMed  Google Scholar 

  91. Koberle B, et al. Elevation of XPA protein level in testis tumor cells without increasing resistance to cisplatin or UV radiation. Mol Carcinog. 2008;47(8):580–6.

    CAS  PubMed  Google Scholar 

  92. Houldsworth J, et al. Human male germ cell tumor resistance to cisplatin is linked to TP53 gene mutation. Oncogene. 1998;16(18):2345–9.

    CAS  PubMed  Google Scholar 

  93. Heimdal K, et al. No germline TP53 mutations detected in familial and bilateral testicular cancer. Genes Chromosomes Cancer. 1993;6(2):92–7.

    CAS  PubMed  Google Scholar 

  94. Peng HQ, et al. Mutations of the p53 gene do not occur in testis cancer. Cancer Res. 1993;53(15):3574–8.

    CAS  PubMed  Google Scholar 

  95. Burger H, et al. Lack of correlation between cisplatin-induced apoptosis, p53 status and expression of Bcl-2 family proteins in testicular germ cell tumour cell lines. Int J Cancer. 1997;73(4):592–9.

    CAS  PubMed  Google Scholar 

  96. Honecker F, et al. Microsatellite instability, mismatch repair deficiency, and BRAF mutation in treatment-resistant germ cell tumors. J Clin Oncol. 2009;27(13):2129–36.

    CAS  PubMed  Google Scholar 

  97. McIntyre A, et al. Activating mutations and/or expression levels of tyrosine kinase receptors GRB7, RAS, and BRAF in testicular germ cell tumors. Neoplasia. 2005;7(12):1047–52.

    CAS  PubMed Central  PubMed  Google Scholar 

  98. Sommerer F, et al. Mutations of BRAF and RAS are rare events in germ cell tumours. Int J Cancer. 2005;113(2):329–35.

    CAS  PubMed  Google Scholar 

  99. Spierings DC, et al. The attractive Achilles heel of germ cell tumours: an inherent sensitivity to apoptosis-inducing stimuli. J Pathol. 2003;200(2):137–48.

    CAS  PubMed  Google Scholar 

  100. Mueller T, et al. Failure of activation of caspase-9 induces a higher threshold for apoptosis and cisplatin resistance in testicular cancer. Cancer Res. 2003;63(2):513–21.

    CAS  PubMed  Google Scholar 

  101. Spierings DC, et al. Loss of drug-induced activation of the CD95 apoptotic pathway in a cisplatin-resistant testicular germ cell tumor cell line. Cell Death Differ. 2003;10(7):808–22.

    CAS  PubMed  Google Scholar 

  102. Koster R, de Jong S. Lessons learned from testicular cancer: identification of cytoplasmic p21 as an Achilles’ heel of cisplatin resistance. Cell Cycle. 2010;9(24):4776–7.

    CAS  PubMed  Google Scholar 

  103. Koster R, et al. Cytoplasmic p21 expression levels determine cisplatin resistance in human testicular cancer. J Clin Invest. 2010;120(10):3594–605.

    CAS  PubMed Central  PubMed  Google Scholar 

  104. Warde P, et al. Prognostic factors for relapse in stage I seminoma managed by surveillance: a pooled analysis. J Clin Oncol. 2002;20(22):4448–52.

    PubMed  Google Scholar 

  105. International Germ Cell Cancer Collaborative Group. International Germ Cell Consensus Classification: a prognostic factor-based staging system for metastatic germ cell cancers. J Clin Oncol. 1997;15(2):594–603.

    Google Scholar 

  106. Noel EE, et al. Identification of genomic changes associated with cisplatin resistance in testicular germ cell tumor cell lines. Genes Chromosomes Cancer. 2008;47(7):604–13.

    CAS  PubMed  Google Scholar 

  107. Paik S, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351(27):2817–26.

    CAS  PubMed  Google Scholar 

  108. Korkola JE, et al. Identification and validation of a gene expression signature that predicts outcome in adult men with germ cell tumors. J Clin Oncol. 2009;27(31):5240–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  109. Ramani P, Yeung CK, Habeebu SS. Testicular intratubular germ cell neoplasia in children and adolescents with intersex. Am J Surg Pathol. 1993;17(11):1124–33.

    CAS  PubMed  Google Scholar 

  110. Rapley EA, et al. A genome-wide association study of testicular germ cell tumor. Nat Genet. 2009;41(7):807–10.

    CAS  PubMed Central  PubMed  Google Scholar 

  111. Feldman DR, Iyer G, Van Alstine L, Patil S, Al-Ahmadie HA, Reuter VE, Bosl GJ, Chaganti RS, Solit DB. Presence of somatic mutations within PIK3CA, AKT, RAS, and FGFR3 but not BRAF in cisplatin-resistant Germ Cell Tumors. Clin Cancer Res. [Epub May 8, 2014].

    Google Scholar 

Download references

Acknowledgments

The reported studies were supported by the Byrne Fund and the Lance Armstrong Foundation.

Author information

Authors and Affiliations

  1. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Darren R. Feldman MD

  2. Department of Medicine and Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    R. S. K. Chaganti PhD

Authors
  1. Darren R. Feldman MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. S. K. Chaganti PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R. S. K. Chaganti PhD .

Editor information

Editors and Affiliations

  1. Department of Urology, Homerton University Hospital & Formerly St. Bartholomew's Hospital, London, United Kingdom

    Vinod H. Nargund

  2. Levine Cancer Institute, Carolinas HealthCare System, Charlotte, North Carolina, USA

    Derek Raghavan

  3. Radiation Oncology, Cedars Sinai Cancer Center, Los Angeles, California, USA

    Howard M. Sandler

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer-Verlag London

About this chapter

Cite this chapter

Feldman, D.R., Chaganti, R.S.K. (2015). Epidemiology, Biology, and Genetics of Adult Male Germ Cell Tumors. In: Nargund, V., Raghavan, D., Sandler, H. (eds) Urological Oncology. Springer, London. https://doi.org/10.1007/978-0-85729-482-1_26

Download citation

  • DOI: https://doi.org/10.1007/978-0-85729-482-1_26

  • Published:

  • Publisher Name: Springer, London

  • Print ISBN: 978-0-85729-481-4

  • Online ISBN: 978-0-85729-482-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation