Cross platform analysis of methylation, miRNA and stem cell gene expression data in germ cell tumors highlights characteristic differences by tumor histology.
BACKGROUND
Alterations in methylation patterns, miRNA expression, and stem cell protein expression occur in germ cell tumors (GCTs). Our goal is to integrate molecular data across platforms to identify molecular signatures in the three main histologic subtypes of Type I and Type II GCTs (yolk sac tumor (YST), germinoma, and teratoma).


METHODS
We included 39 GCTs and 7 paired adjacent tissue samples in the current analysis. Molecular data available for analysis include DNA methylation data (Illumina GoldenGate Cancer Methylation Panel I), miRNA expression (NanoString nCounter miRNA platform), and stem cell factor expression (SABiosciences Human Embryonic Stem Cell Array). We evaluated the cross platform correlations of the data features using the Maximum Information Coefficient (MIC).


RESULTS
In analyses of individual datasets, differences were observed by tumor histology. Germinomas had higher expression of transcription factors maintaining stemness, while YSTs had higher expression of cytokines, endoderm and endothelial markers. We also observed differences in miRNA expression, with miR-371-5p, miR-122, miR-302a, miR-302d, and miR-373 showing elevated expression in one or more histologic subtypes. Using the MIC, we identified correlations across the data features, including six major hubs with higher expression in YST (LEFTY1, LEFTY2, miR302b, miR302a, miR 126, and miR 122) compared with other GCT.


CONCLUSIONS
While prognosis for GCTs is overall favorable, many patients experience resistance to chemotherapy, relapse and/or long term adverse health effects following treatment. Targeted therapies, based on integrated analyses of molecular tumor data such as that presented here, may provide a way to secure high cure rates while reducing unintended health consequences.
Division of Pediatric Epidemiology and Clinical Research, University of Minnesota, Minneapolis, MN, 55455, USA. poynt006@umn.edu.|Masonic Cancer Center, University of Minnesota, Minneapolis, MN, 55455, USA. poynt006@umn.edu.|Corresponding address: 420 Delaware St SE MMC 715, Minneapolis, MN, 55455, USA. poynt006@umn.edu.
Jenny N
JN
Poynter
Division of Pediatric Epidemiology and Clinical Research, University of Minnesota, Minneapolis, MN, 55455, USA. bestra1@stolaf.edu.
Jessica R B M
JR
Bestrashniy
Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN, 55455, USA. kats@umn.edu.
Kevin A T
KA
Silverstein
Masonic Cancer Center, University of Minnesota, Minneapolis, MN, 55455, USA. hoot0006@umn.edu.
Anthony J
AJ
Hooten
Division of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN, 55455, USA. leesx002@umn.edu.
Christopher
C
Lees
Division of Pediatric Epidemiology and Clinical Research, University of Minnesota, Minneapolis, MN, 55455, USA. rossx014@umn.edu.|Masonic Cancer Center, University of Minnesota, Minneapolis, MN, 55455, USA. rossx014@umn.edu.
Julie A
JA
Ross
Masonic Cancer Center, University of Minnesota, Minneapolis, MN, 55455, USA. tolar003@umn.edu.|Division of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN, 55455, USA. tolar003@umn.edu.|Stem Cell Institute, University of Minnesota, Minneapolis, MN, 55455, USA. tolar003@umn.edu.
Jakub
J
Tolar
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation / Q000235:genetics*; D018240:Endodermal Sinus Tumor / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019089:Stem Cell Factor / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism*; D055815:Young Adult
D035683:MicroRNAs; D019089:Stem Cell Factor