Details of Disease

Disease Name

Germ cell tumor

germ cell cancer; malignant tumour of the germ cell; germ cells tumors; germ cells tumours; germ cell neoplasm; tumour of the germ cell; germ cell tumor; tumor of the germ cell; tumour of germ cell; neoplasm of germ cell; neoplasm of the germ cell; tumor of germ cell

Definition

A benign or malignant, gonadal or extragonadal neoplasm that originates from germ cells. Representative examples include teratoma, seminoma, embryonal carcinoma, and yolk sac tumor.

Disease Hierarchy

DISTBY9Z: Tumour

DIS62070: Germ cell tumor

Disease Identifiers

MONDO ID

MONDO_0005040

MESH ID

D009373

UMLS CUI

C0205851

MedGen ID

60030

SNOMED CT ID

115233005

General Information of Disease (ID: DIS62070)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 19 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
FGF4	TTCEKVZ	Limited	Altered Expression	[1]
AFP	TTCFEA1	Strong	Biomarker	[2]
CD9	TTZEIBV	Strong	Biomarker	[3]
DFFA	TTYVQ9C	Strong	Biomarker	[4]
GPC3	TTJTSX4	Strong	Altered Expression	[5]
JAG2	TTOJY1B	Strong	Biomarker	[6]
JUP	TTREN0G	Strong	Biomarker	[7]
KITLG	TTDJ51N	Strong	Genetic Variation	[8]
LIPG	TTHSZXO	Strong	Biomarker	[9]
MAGEA1	TT63M7Q	Strong	Altered Expression	[10]
PDE11A	TTTWC79	Strong	Genetic Variation	[11]
SENP1	TTW9HY5	Strong	Biomarker	[12]
SLAMF7	TT7ILZ1	Strong	Biomarker	[13]
SLC22A3	TTG2UMS	Strong	Biomarker	[14]
SRPK1	TTU3WV6	Strong	Altered Expression	[15]
TDGF1	TTN7HMG	Strong	Altered Expression	[16]
TK1	TTP3QRF	Strong	Genetic Variation	[17]
TKTL1	TTNQ1J3	Strong	Genetic Variation	[17]
TNFRSF8	TT2GM5R	Strong	Biomarker	[18]
------------------------------------------------------------------------------------


⏷ Show the Full List of 19 DTT(s)

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC2A3	DT9SQ3L	Strong	Biomarker	[3]
------------------------------------------------------------------------------------

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
AKR1C1	DE7P2FB	Strong	Biomarker	[19]
------------------------------------------------------------------------------------

This Disease Is Related to 69 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ALPG	OTCIM29R	Limited	Biomarker	[20]
CISH	OT8T5NYL	Limited	Biomarker	[21]
CLEC10A	OTD8HQT6	Limited	Biomarker	[22]
DDX4	OTQOV093	Limited	Biomarker	[23]
DMRT1	OT5PU9U1	Limited	Altered Expression	[24]
GATA6	OTO2BC0F	Limited	Biomarker	[25]
NR5A1	OTOULYR4	Limited	Altered Expression	[26]
SALL4	OTC08PR5	Limited	Altered Expression	[27]
SNRPN	OTQB1ID1	Limited	Biomarker	[28]
AKR1E2	OT7GBQEB	Strong	Altered Expression	[29]
ATRNL1	OTY5JUX2	Strong	Altered Expression	[30]
BCL10	OT47MCLI	Strong	Genetic Variation	[31]
BUB1B	OT8KME51	Strong	Biomarker	[32]
CLSTN1	OTQN35G2	Strong	Biomarker	[13]
CSH1	OT33HTRR	Strong	Biomarker	[13]
CSH2	OTW8JVAN	Strong	Biomarker	[13]
DHDH	OTKA2AL6	Strong	Altered Expression	[19]
DMRT3	OTNV7F7Q	Strong	Altered Expression	[29]
DMRTB1	OT5A94KF	Strong	Biomarker	[33]
DND1	OTHLC8TA	Strong	Genetic Variation	[34]
DPPA3	OTS7N4Q9	Strong	Posttranslational Modification	[35]
EBAG9	OTTQLQCP	Strong	Altered Expression	[36]
EEF1A1	OT00THXS	Strong	Altered Expression	[37]
ENTPD5	OTFH05B9	Strong	Altered Expression	[38]
ESRP1	OTNCS4SL	Strong	Biomarker	[39]
FAM50B	OTP3H38A	Strong	Altered Expression	[40]
GCNA	OTIU3F9Y	Strong	Biomarker	[41]
GDF3	OTD3KGJK	Strong	Altered Expression	[42]
INTS2	OT2N5TCK	Strong	Altered Expression	[43]
ITPRID2	OTO3JDX5	Strong	Biomarker	[13]
KIF7	OT1J6NAW	Strong	Altered Expression	[44]
MAGED4B	OTO37U7W	Strong	Altered Expression	[10]
MAPK15	OT8SW0L7	Strong	Biomarker	[45]
MCF2	OTB9N93T	Strong	Biomarker	[46]
MYOZ2	OTMEIQJA	Strong	Biomarker	[13]
NANOG	OTUEY1FM	Strong	Posttranslational Modification	[47]
NDNF	OTCDL9PG	Strong	Biomarker	[48]
NRIP1	OTIZOJQV	Strong	Biomarker	[49]
NUTM1	OTONYC08	Strong	Altered Expression	[50]
PACC1	OTKBS8CC	Strong	Genetic Variation	[51]
PAGE1	OT7SQGM8	Strong	Biomarker	[52]
PAGE4	OT2VLWT0	Strong	Biomarker	[52]
PDLIM3	OTVXQC81	Strong	Altered Expression	[30]
PEG3	OTHQW98S	Strong	Altered Expression	[53]
PHC1	OT1JMX8U	Strong	Biomarker	[3]
PIGF	OTJKE6VW	Strong	Altered Expression	[54]
PIWIL1	OT7CRGZ3	Strong	Altered Expression	[55]
PIWIL2	OT1PXQIF	Strong	Altered Expression	[56]
PIWIL4	OTDA9MY0	Strong	Altered Expression	[55]
POU5F1	OTDHHN7O	Strong	Altered Expression	[57]
PPP2R2A	OT9297OG	Strong	Biomarker	[58]
PRDM14	OTWZKY4L	Strong	Altered Expression	[59]
PRSS21	OT8ZYC7G	Strong	Biomarker	[60]
PTPN23	OT5WDPXB	Strong	Biomarker	[61]
SCNN1A	OTE2KVZV	Strong	Biomarker	[3]
SNAI3	OTG9DI66	Strong	Altered Expression	[62]
SPANXA1	OTMK3QIS	Strong	Altered Expression	[63]
SPATA6	OTWQQONT	Strong	Biomarker	[64]
SPRY4	OT2VK9N0	Strong	Biomarker	[65]
SRSF5	OTC5WP98	Strong	Altered Expression	[66]
TCF7L1	OTTUTF0O	Strong	Altered Expression	[67]
TK2	OTS1V4XB	Strong	Genetic Variation	[17]
TNFSF8	OTDYGDJ3	Strong	Altered Expression	[68]
TRIP13	OTFM3TI9	Strong	Biomarker	[32]
TSPY1	OTPY57X4	Strong	Genetic Variation	[69]
TSPY3	OTQK3AKI	Strong	Genetic Variation	[69]
ATF7IP	OTU6ZA7F	Definitive	Biomarker	[70]
ERCC1	OTNPYQHI	Definitive	Biomarker	[71]
ERCC4	OTFIOPG1	Definitive	Biomarker	[71]
------------------------------------------------------------------------------------


⏷ Show the Full List of 69 DOT(s)

References

1	Predominant expression of fibroblast growth factor (FGF) 8, FGF4, and FGF receptor 1 in nonseminomatous and highly proliferative components of testicular germ cell tumors.Virchows Arch. 2001 Nov;439(5):616-21. doi: 10.1007/s004280100437.
2	Primary yolk sac tumor originating from the endometrium: A case report and literature review.Medicine (Baltimore). 2019 Apr;98(15):e15144. doi: 10.1097/MD.0000000000015144.
3	Retinoic acid represses a cassette of candidate pluripotency chromosome 12p genes during induced loss of human embryonal carcinoma tumorigenicity. Biochim Biophys Acta. 2005 Oct 15;1731(1):48-56. doi: 10.1016/j.bbaexp.2005.08.006. Epub 2005 Sep 1.
4	Mutations in the N-terminal domain of DFF45 in a primary germ cell tumor and in neuroblastoma tumors.Int J Oncol. 2004 Nov;25(5):1297-302.
5	Immunotherapeutic Targeting of GPC3 in Pediatric Solid Embryonal Tumors.Front Oncol. 2019 Feb 26;9:108. doi: 10.3389/fonc.2019.00108. eCollection 2019.
6	Expression failure of the notch signaling system is associated with the pathogenesis of testicular germ cell tumor.Tumour Biol. 2004 May-Jun;25(3):99-105. doi: 10.1159/000079140.
7	Identification of testicular cancer driver genes by a cross-species comparative oncology approach.Andrology. 2019 Jul;7(4):545-554. doi: 10.1111/andr.12644. Epub 2019 May 13.
8	Association between KITLG Gene Polymorphisms and Testicular Germ Cell Tumors: A Systematic Review and Meta-analysis.Curr Med Sci. 2019 Oct;39(5):702-706. doi: 10.1007/s11596-019-2095-2. Epub 2019 Oct 14.
9	Lipoprotein lipase and endothelial lipase in human testis and in germ cell neoplasms.Int J Androl. 2010 Feb;33(1):e207-15. doi: 10.1111/j.1365-2605.2009.00988.x. Epub 2009 Sep 23.
10	Expression of MAGE genes in testicular germ cell tumors.Urology. 1999 Apr;53(4):843-7. doi: 10.1016/s0090-4295(98)00618-9.
11	Rare inactivating PDE11A variants associated with testicular germ cell tumors.Endocr Relat Cancer. 2015 Dec;22(6):909-17. doi: 10.1530/ERC-15-0034.
12	Chemotherapeutic sensitivity of testicular germ cell tumors under hypoxic conditions is negatively regulated by SENP1-controlled sumoylation of OCT4.Cancer Res. 2012 Oct 1;72(19):4963-73. doi: 10.1158/0008-5472.CAN-12-0673. Epub 2012 Sep 20.
13	Economy of Standards: European Association of Urology Guideline Changes Influence Treatment Costs in Stage I Testicular Cancer Patients.Urol Int. 2018;100(3):279-287. doi: 10.1159/000486343. Epub 2018 Mar 7.
14	Testis-specific protein Y-encoded gene is expressed in early and late stages of gonadoblastoma and testicular carcinoma in situ.Urol Oncol. 2007 Mar-Apr;25(2):141-6. doi: 10.1016/j.urolonc.2006.08.002.
15	Resistance to platinum-containing chemotherapy in testicular germ cell tumors is associated with downregulation of the protein kinase SRPK1.Neoplasia. 2004 Jul-Aug;6(4):297-301. doi: 10.1593/neo.03406.
16	Expression of teratocarcinoma-derived growth factor-1 (TDGF-1) in testis germ cell tumors and its effects on growth and differentiation of embryonal carcinoma cell line NTERA2/D1.Oncogene. 1997 Aug 18;15(8):927-36. doi: 10.1038/sj.onc.1201260.
17	Familial gastrointestinal stromal tumors associated with dysphagia and novel type germline mutation of KIT gene.Gastroenterology. 2002 May;122(5):1493-9. doi: 10.1053/gast.2002.33024.
18	Brentuximab vedotin exerts profound antiproliferative and pro-apoptotic efficacy in CD30-positive as well as cocultured CD30-negative germ cell tumour cell lines.J Cell Mol Med. 2018 Jan;22(1):568-575. doi: 10.1111/jcmm.13344. Epub 2017 Sep 22.
19	Dihydrodiol dehydrogenases regulate the generation of reactive oxygen species and the development of cisplatin resistance in human ovarian carcinoma cells.Cancer Chemother Pharmacol. 2008 May;61(6):979-87. doi: 10.1007/s00280-007-0554-0. Epub 2007 Jul 28.
20	Diagnostic markers for germ cell neoplasms: from placental-like alkaline phosphatase to micro-RNAs.Folia Histochem Cytobiol. 2015;53(3):177-88. doi: 10.5603/FHC.a2015.0020. Epub 2015 Aug 26.
21	Pluripotent Very Small Embryonic-Like Stem Cells in Adult Testes - An Alternate Premise to Explain Testicular Germ Cell Tumors.Stem Cell Rev Rep. 2018 Dec;14(6):793-800. doi: 10.1007/s12015-018-9848-3.
22	Expression patterns of transcribed human endogenous retrovirus HERV-K(HML-2) loci in human tissues and the need for a HERV Transcriptome Project.BMC Genomics. 2008 Jul 29;9:354. doi: 10.1186/1471-2164-9-354.
23	VASA is a specific marker for both normal and malignant human germ cells.Lab Invest. 2002 Feb;82(2):159-66. doi: 10.1038/labinvest.3780408.
24	Protein expression of the transcription factors DMRT1, TCLF5, and OCT4 in selected germ cell neoplasms of the testis.Hum Pathol. 2018 Dec;82:68-75. doi: 10.1016/j.humpath.2018.07.019. Epub 2018 Jul 29.
25	Transcription factors GATA-4 and GATA-6, and their potential downstream effectors in ovarian germ cell tumors.Tumour Biol. 2005 Sep-Oct;26(5):265-73. doi: 10.1159/000087565. Epub 2005 Aug 17.
26	Evaluation of SF-1 expression in testicular germ cell tumors: a tissue microarray study of 127 cases.Appl Immunohistochem Mol Morphol. 2013 Jul;21(4):318-21. doi: 10.1097/PAI.0b013e318277cf5a.
27	Functional and clinical significance of SALL4 in breast cancer.Tumour Biol. 2016 Sep;37(9):11701-11709. doi: 10.1007/s13277-016-5150-7. Epub 2016 Jul 21.
28	Multipoint imprinting analysis indicates a common precursor cell for gonadal and nongonadal pediatric germ cell tumors.Cancer Res. 2001 Oct 1;61(19):7268-76.
29	Identification of a TSPY co-expression network associated with DNA hypomethylation and tumor gene expression in somatic cancers.J Genet Genomics. 2016 Oct 20;43(10):577-585. doi: 10.1016/j.jgg.2016.09.003. Epub 2016 Sep 17.
30	Expression of the germ cell alkaline phosphatase gene in human choriocarcinoma cells.J Biol Chem. 1989 Jul 25;264(21):12611-9.
31	Association of BCL10 germ line polymorphisms on chromosome 1p with advanced stage testicular germ cell tumor patients.Cancer Lett. 2006 Aug 18;240(1):41-7. doi: 10.1016/j.canlet.2005.08.019. Epub 2005 Oct 17.
32	Biallelic TRIP13 mutations predispose to Wilms tumor and chromosome missegregation. Nat Genet. 2017 Jul;49(7):1148-1151. doi: 10.1038/ng.3883. Epub 2017 May 29.
33	Immunolocalization of DMRTB1 in human testis with normal and impaired spermatogenesis.Andrology. 2019 Jul;7(4):428-440. doi: 10.1111/andr.12617. Epub 2019 Mar 28.
34	Analysis of the DND1 gene in men with sporadic and familial testicular germ cell tumors.Genes Chromosomes Cancer. 2008 Mar;47(3):247-52. doi: 10.1002/gcc.20526.
35	Imprints and DPPA3 are bypassed during pluripotency- and differentiation-coupled methylation reprogramming in testicular germ cell tumors.Genome Res. 2016 Nov;26(11):1490-1504. doi: 10.1101/gr.201293.115. Epub 2016 Oct 20.
36	Estrogen receptor-binding fragment-associated gene 9 expression and its clinical significance in human testicular cancer.Int J Urol. 2009 Mar;16(3):329-32. doi: 10.1111/j.1442-2042.2008.02233.x. Epub 2009 Jan 20.
37	The human Y-encoded testis-specific protein interacts functionally with eukaryotic translation elongation factor eEF1A, a putative oncoprotein.Int J Cancer. 2008 Oct 1;123(7):1573-85. doi: 10.1002/ijc.23697.
38	PCPH expression is an early event in the development of testicular germ cell tumors.Int J Oncol. 2006 Mar;28(3):595-604.
39	Esrp1 is a marker of mouse fetal germ cells and differentially expressed during spermatogenesis.PLoS One. 2018 Jan 11;13(1):e0190925. doi: 10.1371/journal.pone.0190925. eCollection 2018.
40	Novel retrotransposed imprinted locus identified at human 6p25.Nucleic Acids Res. 2011 Jul;39(13):5388-400. doi: 10.1093/nar/gkr108. Epub 2011 Mar 18.
41	GCNA Preserves Genome Integrity and Fertility Across Species.Dev Cell. 2020 Jan 6;52(1):38-52.e10. doi: 10.1016/j.devcel.2019.11.007. Epub 2019 Dec 12.
42	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. 2009 Aug;22(8):1066-74. doi: 10.1038/modpathol.2009.66. Epub 2009 Apr 24.
43	Expression of the hst-1 and c-kit protooncogenes in human testicular germ cell tumors.Cancer Res. 1991 Apr 1;51(7):1811-6.
44	Characterization of KIF7 gene in silico.Int J Oncol. 2004 Dec;25(6):1881-6.
45	MAPK15 upregulation promotes cell proliferation and prevents DNA damage in male germ cell tumors.Oncotarget. 2016 Apr 12;7(15):20981-98. doi: 10.18632/oncotarget.8044.
46	Mutational analysis of proto-oncogene Dbl on Xq27 in testicular germ cell tumors reveals a rare SNP in a patient with bilateral undescended testis.World J Urol. 2009 Dec;27(6):811-5. doi: 10.1007/s00345-009-0408-y.
47	NANOG promoter methylation and expression correlation during normal and malignant human germ cell development.Epigenetics. 2011 Jan;6(1):114-22. doi: 10.4161/epi.6.1.13433. Epub 2011 Jan 1.
48	Parental Occupational Exposure to Organic Solvents and Testicular Germ Cell Tumors in their Offspring: NORD-TEST Study.Environ Health Perspect. 2017 Jun 30;125(6):067023. doi: 10.1289/EHP864.
49	Selective repression of retinoic acid target genes by RIP140 during induced tumor cell differentiation of pluripotent human embryonal carcinoma cells.Mol Cancer. 2007 Sep 19;6:57. doi: 10.1186/1476-4598-6-57.
50	Nuclear protein in testis midline carcinomas: a lethal and underrecognized entity.Arch Pathol Lab Med. 2011 Nov;135(11):1494-8. doi: 10.5858/arpa.2010-0389-CR.
51	A 3-Mb high-resolution BAC/PAC contig of 12q22 encompassing the 830-kb consensus minimal deletion in male germ cell tumors.Genome Res. 1999 Jul;9(7):662-71.
52	PAGE-1, an X chromosome-linked GAGE-like gene that is expressed in normal and neoplastic prostate, testis, and uterus.Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10757-62. doi: 10.1073/pnas.95.18.10757.
53	Loss of miR-514a-3p regulation of PEG3 activates the NF-kappa B pathway in human testicular germ cell tumors.Cell Death Dis. 2017 May 4;8(5):e2759. doi: 10.1038/cddis.2016.464.
54	Neovascularization in human germ cell tumors correlates with a marked increase in the expression of the vascular endothelial growth factor but not the placenta-derived growth factor.Oncogene. 1996 Aug 1;13(3):577-87.
55	Differential Regulation of PIWI-LIKE 2 Expression in Primordial Germ Cell Tumor Cell Lines by Promoter Methylation.Front Genet. 2018 Sep 20;9:375. doi: 10.3389/fgene.2018.00375. eCollection 2018.
56	Expression profiles of PIWIL2 short isoforms differ in testicular germ cell tumors of various differentiation subtypes.PLoS One. 2014 Nov 10;9(11):e112528. doi: 10.1371/journal.pone.0112528. eCollection 2014.
57	Potential Role of OCT4 in Leukemogenesis.Stem Cells Dev. 2017 Nov 15;26(22):1637-1647. doi: 10.1089/scd.2017.0134. Epub 2017 Oct 16.
58	Fusion of the tumor-suppressor gene CHEK2 and the gene for the regulatory subunit B of protein phosphatase 2 PPP2R2A in childhood teratoma.Neoplasia. 2006 May;8(5):413-8. doi: 10.1593/neo.06139.
59	PRDM14 is expressed in germ cell tumors with constitutive overexpression altering human germline differentiation and proliferation.Stem Cell Res. 2018 Mar;27:46-56. doi: 10.1016/j.scr.2017.12.016. Epub 2018 Jan 4.
60	Epigenetic silencing of the putative tumor suppressor gene testisin in testicular germ cell tumors.J Cancer Res Clin Oncol. 2006 Dec;132(12):765-70. doi: 10.1007/s00432-006-0124-6. Epub 2006 Jun 21.
61	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. 2013 Aug 16;288(33):23990-9. doi: 10.1074/jbc.M113.478891. Epub 2013 Jul 10.
62	Identification and characterization of human SNAIL3 (SNAI3) gene in silico.Int J Mol Med. 2003 Mar;11(3):383-8.
63	Expression of SpanX mRNA in testicular germ cell tumors.Hum Cell. 2006 Aug;19(3):87-90. doi: 10.1111/j.1749-0774.2006.00014.x.
64	The role of spermatogenesis-associated protein 6 in testicular germ cell tumors.Int J Clin Exp Pathol. 2015 Aug 1;8(8):9119-25. eCollection 2015.
65	Variants in BAK1, SPRY4, and GAB2 are associated with pediatric germ cell tumors: A report from the children's oncology group.Genes Chromosomes Cancer. 2017 Jul;56(7):548-558. doi: 10.1002/gcc.22457. Epub 2017 Apr 4.
66	TRPV4-dependent induction of a novel mammalian cold-inducible protein SRSF5 as well as CIRP and RBM3.Sci Rep. 2017 May 23;7(1):2295. doi: 10.1038/s41598-017-02473-x.
67	Wnt suppressor and stem cell regulator TCF7L1 is a sensitive immunohistochemical marker to differentiate testicular seminoma from non-seminomatous germ cell tumor.Exp Mol Pathol. 2019 Oct;110:104293. doi: 10.1016/j.yexmp.2019.104293. Epub 2019 Aug 2.
68	Expression of CD30 and CD30 ligand in cultured cell lines from human germ-cell tumors.Lab Invest. 1997 Apr;76(4):497-504.
69	SRY mutation analysis by next generation (deep) sequencing in a cohort of chromosomal Disorders of Sex Development (DSD) patients with a mosaic karyotype.BMC Med Genet. 2012 Nov 16;13:108. doi: 10.1186/1471-2350-13-108.
70	Variants near DMRT1, TERT and ATF7IP are associated with testicular germ cell cancer.Nat Genet. 2010 Jul;42(7):604-7. doi: 10.1038/ng.607. Epub 2010 Jun 13.
71	ERCC1 and XPF expression in human testicular germ cell tumors.Oncol Rep. 2010 Jan;23(1):223-7.