The Epigenetics of Testicular Germ Cell Tumors: Looking for Novel Disease Biomarkers

References

• Ferlay J , SoerjomataramI , DikshitRet al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012 . Int. J. Cancer136 ( 5 ), E359 – E386 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Oosterhuis JW , LooijengaLH . Testicular germ-cell tumours in a broader perspective . Nat. Rev. Cancer5 ( 3 ), 210 – 222 ( 2005 ).
   PubMed Web of Science ®Google Scholar
• Trabert B , ChenJ , DevesaSS , BrayF , McglynnKA . International patterns and trends in testicular cancer incidence, overall and by histologic subtype, 1973–2007 . Andrology3 ( 1 ), 4 – 12 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Howlader N , NooneAM , KrapchoMet al. SEER Cancer Statistics Review, 1975–2013, National Cancer Institute . Bethesda, MD . http://seer.cancer.gov/csr/1975_2013/ .
   Google Scholar
• Rijlaarsdam MA , LooijengaLH . An oncofetal and developmental perspective on testicular germ cell cancer . Semin. Cancer Biol.29 , 59 – 74 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Stevenson SM , LowranceWT . Epidemiology and Diagnosis of Testis Cancer . Urol. Clin. North Am.42 ( 3 ), 269 – 275 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Hanna NH , EinhornLH . Testicular cancer-discoveries and updates . N. Engl. J. Med.371 ( 21 ), 2005 – 2016 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Feldman DR . Update in germ cell tumours . Curr. Opin. Oncol.27 ( 3 ), 177 – 184 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Rajpert-De Meyts E , McglynnKA , OkamotoK , JewettMA , BokemeyerC . Testicular germ cell tumours . Lancet387 ( 10029 ), 1762 – 1774 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Curreri SA , FungC , BeardCJ . Secondary malignant neoplasms in testicular cancer survivors . Urol. Oncol.33 ( 9 ), 392 – 398 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Beyer J , AlbersP , AltenaRet al. Maintaining success, reducing treatment burden, focusing on survivorship: highlights from the third European consensus conference on diagnosis and treatment of germ-cell cancer . Ann. Oncol.24 ( 4 ), 878 – 888 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Kollmannsberger C , TandstadT , BedardPLet al. Patterns of relapse in patients with clinical stage I testicular cancer managed with active surveillance . J. Clin. Oncol.33 ( 1 ), 51 – 57 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Mir MC , PavanN , GonzalgoML . Current clinical applications of testicular cancer biomarkers . Urol. Clin. North Am.43 ( 1 ), 119 – 125 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Howitt BE , BerneyDM . Tumors of the testis: morphologic features and molecular alterations . Surg. Pathol. Clin.8 ( 4 ), 687 – 716 ( 2015 ).
   PubMedGoogle Scholar
• Krege S , BeyerJ , SouchonRet al. European consensus conference on diagnosis and treatment of germ cell cancer: a report of the second meeting of the European Germ Cell Cancer Consensus Group (EGCCCG): part I . Eur. Urol.53 ( 3 ), 478 – 496 ( 2008 ).
   PubMedGoogle Scholar
• Sharma P , DhillonJ , AgarwalG , Zargar-ShoshtariK , SextonWJ . Disparities in interpretation of primary testicular germ cell tumor pathology . Am. J. Clin. Pathol.144 ( 2 ), 289 – 294 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Satish K Tickoo , ReuterVE , MahulB Aminet al. Protocol for the examination of specimens from patients with malignant germ cell and sex cord stromal tumors of the testis . Arch. Pathol. Lab. Med.123 ( 1 ), 14 – 19 ( 2013 ).
   Google Scholar
• Gopalan A , DhallD , OlgacSet al. Testicular mixed germ cell tumors: a morphological and immunohistochemical study using stem cell markers, OCT3/4, SOX2 and GDF3, with emphasis on morphologically difficult-to-classify areas . Mod. Pathol.22 ( 8 ), 1066 – 1074 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Moch H , CubillaAL , HumphreyPA , ReuterVE , UlbrightTM . The 2016 WHO classification of tumours of the urinary system and male genital organs-Part A: renal, penile, and testicular tumours . Eur. Urol.70 ( 1 ), 93 – 105 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Holger Moch PaH , ThomasM Ulbright , VictorE Reuter . Who Classification of Tumours of the Urinary System and Male Genital Organs (4th Edition) . IARC , Lyon ( 2016 ).
   Google Scholar
• Litchfield K , LevyM , HuddartRA , ShipleyJ , TurnbullC . The genomic landscape of testicular germ cell tumours: from susceptibility to treatment . Nat. Rev. Urol.13 ( 7 ), 409 – 419 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Berney DM , LooijengaL , IdreesMet al. Germ cell neoplasia in situ (GCNIS). Evolution of the current nomenclature for testicular pre-invasive germ cell malignancy . Histopathology69 ( 1 ), 7 – 10 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Masterson TA , RiceKR , BeckSD . Current and future biologic markers for disease progression and relapse in testicular germ cell tumors: a review . Urol. Oncol.32 ( 3 ), 261 – 271 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Belge G , DieckmannK-P , SpiekermannM , BalksT , BullerdiekJ . Serum levels of microRNAs miR-371–3: a novel class of serum biomarkers for testicular germ cell tumors?Eur. Urol.61 ( 5 ), 1068 – 1069 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Ellinger J , AlbersP , PeraboFG , MüllerSC , Von RueckerA , BastianPJ . CpG island hypermethylation of cell-free circulating serum DNA in patients with testicular cancer . J. Urol.182 ( 1 ), 324 – 329 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Syring I , BartelsJ , HoldenriederS , KristiansenG , MüllerSC , EllingerJ . Circulating serum miRNA (miR-367–3p, miR-371a-3p, miR-372–3p and miR-373–3p) as biomarkers in patients with testicular germ cell cancer . J. Urol.193 ( 1 ), 331 – 337 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Murray MJ , BellE , RabyKLet al. A pipeline to quantify serum and cerebrospinal fluid microRNAs for diagnosis and detection of relapse in paediatric malignant germ-cell tumours . Br. J. Cancer114 ( 2 ), 151 – 162 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Murray MJ , ColemanN . Testicular cancer: a new generation of biomarkers for malignant germ cell tumours . Nat. Rev. Urol.9 ( 6 ), 298 – 300 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Wermann H , StoopH , GillisAJet al. Global DNA methylation in fetal human germ cells and germ cell tumours: association with differentiation and cisplatin resistance . J. Pathol.221 ( 4 ), 433 – 442 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Smiraglia DJ , SzymanskaJ , KraggerudSM , LotheRA , PeltomakiP , PlassC . Distinct epigenetic phenotypes in seminomatous and nonseminomatous testicular germ cell tumors . Oncogene21 ( 24 ), 3909 – 3916 ( 2002 ).
   PubMed Web of Science ®Google Scholar
• Almstrup K , NielsenJ , MlynarskaOet al. Carcinoma in situ testis displays permissive chromatin modifications similar to immature foetal germ cells . Br. J. Cancer103 ( 8 ), 1269 – 1276 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Netto GJ , NakaiY , NakayamaMet al. Global DNA hypomethylation in intratubular germ cell neoplasia and seminoma, but not in nonseminomatous male germ cell tumors . Mod. Pathol.21 ( 11 ), 1337 – 1344 ( 2008 ).
   PubMed Web of Science ®Google Scholar
• Koul S , HouldsworthJ , MansukhaniMMet al. Characteristic promoter hypermethylation signatures in male germ cell tumors . Mol. Cancer1 ( 1 ), 1 ( 2002 ).
   Google Scholar
• Kawakami T , OkamotoK , OgawaO , OkadaY . XISTunmethylated DNA fragments in male-derived plasma as a tumour marker for testicular cancer . The Lancet363 ( 9402 ), 40 – 42 ( 2004 ).
   PubMed Web of Science ®Google Scholar
• Koul S , MckiernanJM , NarayanGet al. Role of promoter hypermethylation in cisplatin treatment response of male germ cell tumors . Mol. Cancer3 ( 1 ), 1 ( 2004 ).
   PubMedGoogle Scholar
• Smith-S⊘rensen B , LindG , SkotheimRet al. Frequent promoter hypermethylation of the O 6-methylguanine-DNA methyltransferase (MGMT) gene in testicular cancer . J. Urol.175 ( 1 ), 154 – 155 ( 2006 ).
   Google Scholar
• Martinelli CM , LengertAV , CarcanoFMet al. MGMT and CALCA promoter methylation are associated with poor prognosis in testicular germ cell tumor patients . Oncotarget doi:10.18632/oncotarget.11167 ( 2016 ) ( Epub ahead of print ).
   Google Scholar
• Lind G , SkotheimR , FragaM , AbelerV , EstellerM , LotheR . Novel epigenetically deregulated genes in testicular cancer include homeobox genes and SCGB3A1 (HIN-1) . J. Pathol.210 ( 4 ), 441 – 449 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Cheung H-H , YangY , LeeT-L , RennertO , ChanW-Y . Hypermethylation of genes in testicular embryonal carcinomas . Br. J. Cancer114 ( 2 ), 230 – 236 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Spiller CM , GillisAJ , BurnetGet al. Cripto: expression, epigenetic regulation and potential diagnostic use in testicular germ cell tumors . Mol. Oncol.10 ( 4 ), 526 – 537 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Spiller CM , BowlesJ , KoopmanP . Nodal/cripto signaling in fetal male germ cell development: implications for testicular germ cell tumors . Int. J. Dev. Biol.57 ( 2–4 ), 211 – 219 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Shen MM . Nodal signaling: developmental roles and regulation . Development134 ( 6 ), 1023 – 1034 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Amatruda JF , RossJA , ChristensenBet al. DNA methylation analysis reveals distinct methylation signatures in pediatric germ cell tumors . BMC Cancer13 ( 1 ), 1 ( 2013 ).
   PubMedGoogle Scholar
• Kato N , TamuraG , FukaseM , ShibuyaH , MotoyamaT . Hypermethylation of the RUNX3 gene promoter in testicular yolk sac tumor of infants . Am. J. Pathol.163 ( 2 ), 387 – 391 ( 2003 ).
   PubMed Web of Science ®Google Scholar
• Kato N , ShibuyaH , FukaseM , TamuraG , MotoyamaT . Involvement of adenomatous polyposis coli (APC) gene in testicular yolk sac tumor of infants . Hum. Pathol.37 ( 1 ), 48 – 53 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Lander ES , LintonLM , BirrenBet al. Initial sequencing and analysis of the human genome . Nature409 ( 6822 ), 860 – 921 ( 2001 ).
   PubMed Web of Science ®Google Scholar
• Wilson AS , PowerBE , MolloyPL . DNA hypomethylation and human diseases . Biochim. Biophys. Acta1775 ( 1 ), 138 – 162 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Ushida H , KawakamiT , MinamiKet al. Methylation profile of DNA repetitive elements in human testicular germ cell tumor . Mol. Carcinog.51 ( 9 ), 711 – 722 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Kohli RM , ZhangY . TET enzymes, TDG and the dynamics of DNA demethylation . Nature502 ( 7472 ), 472 – 479 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Munari E , ChauxA , VaghasiaAMet al. Global 5-hydroxymethylcytosine levels are profoundly reduced in multiple genitourinary malignancies . PLoS ONE11 ( 1 ), e0146302 ( 2016 ).
   PubMed Web of Science ®Google Scholar
• Haffner MC , ChauxA , MeekerAKet al. Global 5-hydroxymethylcytosine content is significantly reduced in tissue stem/progenitor cell compartments and in human cancers . Oncotarget2 ( 8 ), 627 – 637 ( 2011 ).
   PubMedGoogle Scholar
• Jin S-G , JiangY , QiuRet al. 5-Hydroxymethylcytosine is strongly depleted in human cancers but its levels do not correlate with IDH1 mutations . Cancer Res.71 ( 24 ), 7360 – 7365 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Koychev D , OechsleK , BokemeyerC , HoneckerF . Treatment of patients with relapsed and/or cisplatin-refractory metastatic germ cell tumours: an update . Int. J. Androl.34 ( 4pt2 ), e266 – e273 ( 2011 ).
   PubMedGoogle Scholar
• Liu L , LianJ , ZhangHet al. MicroRNA-302a sensitizes testicular embryonal carcinoma cells to cisplatin-induced cell death . J. Cell. Physiol.228 ( 12 ), 2294 – 2304 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Füllgrabe J , KavanaghE , JosephB . Histone onco-modifications . Oncogene30 ( 31 ), 3391 – 3403 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Faure A , Pivot-PajotC , KerjeanAet al. Misregulation of histone acetylation in Sertoli cell-only syndrome and testicular cancer . Mol. Hum. Reprod.9 ( 12 ), 757 – 763 ( 2003 ).
   PubMed Web of Science ®Google Scholar
• Kristensen DG , MlynarskaO , NielsenJE , JacobsenGK , Rajpert-DeMeyts E , AlmstrupK . Heterogeneity of chromatin modifications in testicular spermatocytic seminoma point toward an epigenetically unstable phenotype . Cancer Genet.205 ( 9 ), 425 – 431 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Lambrot R , KimminsS . Histone methylation is a critical regulator of the abnormal expression of POU5F1 and RASSF1A in testis cancer cell lines . Int. J. Androl.34 ( 2 ), 110 – 123 ( 2011 ).
   PubMedGoogle Scholar
• Looijenga LH , StoopH , De LeeuwHPet al. POU5F1 (OCT3/4) identifies cells with pluripotent potential in human germ cell tumors . Cancer Res.63 ( 9 ), 2244 – 2250 ( 2003 ).
   PubMed Web of Science ®Google Scholar
• Palumbo C , Van RoozendaalK , GillisAJet al. Expression of the PDGF α-receptor 1.5 kb transcript, OCT-4, and c-KIT in human normal and malignant tissues. Implications for the early diagnosis of testicular germ cell tumours and for our understanding of regulatory mechanisms . J. Pathol.196 ( 4 ), 467 – 477 ( 2002 ).
   PubMed Web of Science ®Google Scholar
• Esteller M . Non-coding RNAs in human disease . Nat. Rev. Genet.12 ( 12 ), 861 – 874 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Ferreira HJ , HeynH , Garcia Del MuroXet al. Epigenetic loss of the PIWI/piRNA machinery in human testicular tumorigenesis . Epigenetics9 ( 1 ), 113 – 118 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Rounge T , FuruK , SkotheimR , HaugenT , GrotmolT , EnerlyE . Profiling of the small RNA populations in human testicular germ cell tumors shows global loss of piRNAs . Mol. Cancer14 ( 1 ), 1 ( 2015 ).
   PubMedGoogle Scholar
• Gainetdinov IV , KondratievaSA , SkvortsovaYVet al. Distinguishing epigenetic features of preneoplastic testis tissues adjacent to seminomas and nonseminomas . Biomarkers3 , 4 ( 2016 ).
   Google Scholar
• Garzon R , CalinGA , CroceCM . MicroRNAs in cancer . Annu. Rev. Med.60 , 167 – 179 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Palmer RD , MurrayMJ , SainiHKet al. Malignant germ cell tumors display common microRNA profiles resulting in global changes in expression of messenger RNA targets . Cancer Res.70 ( 7 ), 2911 – 2923 ( 2010 ).
   PubMed Web of Science ®Google Scholar
• Calin GA , CroceCM . MicroRNA signatures in human cancers . Nat. Rev. Cancer6 ( 11 ), 857 – 866 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Novotny GW , SonneS , NielsenJEet al. Translational repression of E2F1 mRNA in carcinoma in situ and normal testis correlates with expression of the miR-17–92 cluster . Cell Death Differ.14 ( 4 ), 879 – 882 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Voorhoeve PM , Le SageC , SchrierMet al. A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors . Cell124 ( 6 ), 1169 – 1181 ( 2006 ).
   PubMed Web of Science ®Google Scholar
• Tanaka K , KondoK , KitajimaK , MuraokaM , NozawaA , HaraT . Tumor-suppressive function of protein-tyrosine phosphatase non-receptor type 23 in testicular germ cell tumors is lost upon overexpression of miR142–3p microRNA . J. Biol. Chem.288 ( 33 ), 23990 – 23999 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Gillis A , StoopH , HersmusRet al. High-throughput microRNAome analysis in human germ cell tumours . J. Pathol.213 ( 3 ), 319 – 328 ( 2007 ).
   PubMed Web of Science ®Google Scholar
• Murray MJ , SainiHK , Van DongenSet al. The two most common histological subtypes of malignant germ cell tumour are distinguished by global microRNA profiles, associated with differential transcription factor expression . Mol. Cancer9 ( 1 ), 1 ( 2010 ).
   PubMedGoogle Scholar
• Novotny GW , BellingKC , BramsenJBet al. MicroRNA expression profiling of carcinoma in situ cells of the testis . Endocr. Relat. Cancer19 ( 3 ), 365 – 379 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Murray MJ , HalsallDJ , HookCE , WilliamsDM , NicholsonJC , ColemanN . Identification of microRNAs from the miR-371∼ 373 and miR-302 clusters as potential serum biomarkers of malignant germ cell tumors . Am. J. Clin. Pathol.135 ( 1 ), 119 – 125 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Gillis AJ , RijlaarsdamMA , EiniRet al. Targeted serum miRNA (TSmiR) test for diagnosis and follow-up of (testicular) germ cell cancer patients: a proof of principle . Mol. Oncol.7 ( 6 ), 1083 – 1092 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Dieckmann K , SpiekermannM , BalksTet al. MicroRNAs miR-371–3 in serum as diagnostic tools in the management of testicular germ cell tumours . Br. J. Cancer107 ( 10 ), 1754 – 1760 ( 2012 ).
   PubMed Web of Science ®Google Scholar
• Spiekermann M , BelgeG , WinterNet al. MicroRNA miR-371a-3p in serum of patients with germ cell tumours: evaluations for establishing a serum biomarker . Andrology3 ( 1 ), 78 – 84 ( 2015 ).
   PubMed Web of Science ®Google Scholar
• Dieckmann KP , RadtkeA , SpiekermannMet al. Serum levels of microRNA miR-371a-3p: a sensitive and specific new biomarker for germ cell tumours . Eur. Urol. doi:10.1016/j.eururo.2016.07.029 ( 2016 ) ( Epub ahead of print ).
   PubMed Web of Science ®Google Scholar
• Port M , GlaesenerS , RufCet al. Micro-RNA expression in cisplatin resistant germ cell tumor cell lines . Mol. Cancer10 ( 1 ), 1 ( 2011 ).
   PubMedGoogle Scholar
• Cheung H , DavisA , LeeTet al. Methylation of an intronic region regulates miR-199a in testicular tumor malignancy . Oncogene30 ( 31 ), 3404 – 3415 ( 2011 ).
   PubMed Web of Science ®Google Scholar
• Gu S , CheungHH , LeeTL , LuG , PoonWS , ChanWY . Molecular mechanisms of regulation and action of microRNA-199a in testicular germ cell tumor and glioblastomas . PLoS ONE8 ( 12 ), e83980 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• Chen B-F , GuS , SuenY-K , LiL , ChanW-Y . microRNA-199a-3p, DNMT3A, and aberrant DNA methylation in testicular cancer . Epigenetics9 ( 1 ), 119 – 128 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Chen B-F , SuenY-K , GuS , LiL , ChanW-Y . A miR-199a/miR-214 self-regulatory network via PSMD10, TP53 and DNMT1 in testicular germ cell tumor . Sci. Rep.4 , 6413 ( 2014 ).
   PubMed Web of Science ®Google Scholar
• Murray MJ , SainiHK , SieglerCAet al. LIN28 expression in malignant germ cell tumors downregulates let-7 and increases oncogene levels . Cancer Res.73 ( 15 ), 4872 – 4884 ( 2013 ).
   PubMed Web of Science ®Google Scholar
• West JA , ViswanathanSR , YabuuchiAet al. A role for Lin28 in primordial germ-cell development and germ-cell malignancy . Nature460 ( 7257 ), 909 – 913 ( 2009 ).
   PubMed Web of Science ®Google Scholar
• Purshouse K , WatsonRA , ChurchDNet al. Value of supraregional multidisciplinary review for the contemporary management of testicular tumors . Clin. Genitourin. Cancer doi:10.1016/j.clgc.2016.05.005 ( 2016 ) ( Epub ahead of print ).
   PubMed Web of Science ®Google Scholar
• Poynter JN , BestrashniyJR , SilversteinKAet al. Cross platform analysis of methylation, miRNA and stem cell gene expression data in germ cell tumors highlights characteristic differences by tumor histology . BMC Cancer15 ( 1 ), 769 ( 2015 ).
   PubMedGoogle Scholar
• Aoun F , KourieHR , AlbisinniS , RoumeguereT . Will testicular germ cell tumors remain untargetable?Target. Oncol. doi:10.1007/s11523-016-0439-4 ( 2016 ) ( Epub ahead of print ).
   PubMed Web of Science ®Google Scholar