STANDARD_NAME	KORKOLA_YOLK_SAC_TUMOR_UP
SYSTEMATIC_NAME	M18161
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KORKOLA_YOLK_SAC_TUMOR_UP
NAMESPACE	AFFY_HG_U133
DESCRIPTION_BRIEF	Genes from the 12p region that were up-regulated in yolk sac tumor cells compared to normal testis.
DESCRIPTION_FULL	Adult male germ cell tumors (GCTs) comprise distinct groups: seminomas and nonseminomas, which include pluripotent embryonal carcinomas as well as other histologic subtypes exhibiting various stages of differentiation. Almost all GCTs show 12p gain, but the target genes have not been clearly defined. To identify 12p target genes, we examined Affymetrix (Santa Clara, CA) U133A+B microarray ( approximately 83% coverage of 12p genes) expression profiles of 17 seminomas, 84 nonseminoma GCTs, and 5 normal testis samples. Seventy-three genes on 12p were significantly overexpressed, including GLUT3 and REA (overexpressed in all GCTs) and CCND2 and FLJ22028 (overexpressed in all GCTs, except choriocarcinomas). We characterized a 200-kb gene cluster at 12p13.31 that exhibited coordinated overexpression in embryonal carcinomas and seminomas, which included the known stem cell genes NANOG, STELLA, and GDF3 and two previously uncharacterized genes. A search for other coordinately regulated genomic clusters of stem cell genes did not reveal any genomic regions similar to that at 12p13.31. Comparison of embryonal carcinoma with seminomas revealed relative overexpression of several stem cell-associated genes in embryonal carcinoma, including several core stemness genes (EBAF, TDGF1, and SOX2) and several downstream targets of WNT, NODAL, and FGF signaling (FGF4, NODAL, and ZFP42). Our results indicate that 12p gain is a functionally relevant change leading to activation of proliferation and reestablishment/maintenance of stem cell function through activation of key stem cell genes. Furthermore, the differential expression of core stem cell genes may explain the differences in pluripotency between embryonal carcinomas and seminomas.
PMID	16424014
GEOID	GSE3218
AUTHORS	Korkola JE,Houldsworth J,Chadalavada RS,Olshen AB,Dobrzynski D,Reuter VE,Bosl GJ,Chaganti RS
CONTRIBUTOR	Arthur Liberzon
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Table 3S
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	200951_s_at,200953_s_at,201030_x_at,201600_at,202499_s_at,204375_at,206687_s_at,212918_at,213011_s_at,213615_at,218045_x_at,218102_at,218470_at,218894_s_at,220147_s_at,220890_s_at,225745_at,225963_at,232816_s_at,41037_at,AFFX-HUMGAPDH/M33197_3_at
GENE_SYMBOLS	CCND2,CCND2,LDHB,PHB2,SLC2A3,CLSTN3,PTPN6,RECQL,TPI1,EMG1,PTMS,DERA,YARS2,MAGOHB,SINHCAF,DDX47,LRP6,KLHL42,DDX11,TEAD4,GAPDH
FOUNDER_NAMES