Malignant germ cell tumors display common microRNA profiles resulting in global changes in expression of messenger RNA targets.

Abstract:

:Despite their extensive clinical and pathologic heterogeneity, all malignant germ cell tumors (GCT) are thought to originate from primordial germ cells. However, no common biological abnormalities have been identified to date. We profiled 615 microRNAs (miRNA) in pediatric malignant GCTs, controls, and GCT cell lines (48 samples in total) and re-analyzed available miRNA expression data in adult gonadal malignant GCTs. We applied the bioinformatic algorithm Sylamer to identify miRNAs that are of biological importance by inducing global shifts in mRNA levels. The most significant differentially expressed miRNAs in malignant GCTs were all from the miR-371-373 and miR-302 clusters (adjusted P < 0.00005), which were overexpressed regardless of histologic subtype [yolk sac tumor (YST)/seminoma/embryonal carcinoma (EC)], site (gonadal/extragonadal), or patient age (pediatric/adult). Sylamer revealed that the hexamer GCACTT, complementary to the 2- to 7-nucleotide miRNA seed AAGUGC shared by six members of the miR-371-373 and miR-302 clusters, was the only sequence significantly enriched in the 3'-untranslated region of mRNAs downregulated in pediatric malignant GCTs (as a group), YSTs and ECs, and in adult YSTs (all versus nonmalignant tissue controls; P < 0.05). For the pediatric samples, downregulated genes containing the 3'-untranslated region GCACTT showed significant overrepresentation of Gene Ontology terms related to cancer-associated processes, whereas for downregulated genes lacking GCACTT, Gene Ontology terms generally represented metabolic processes only, with few genes per term (adjusted P < 0.05). We conclude that the miR-371-373 and miR-302 clusters are universally overexpressed in malignant GCTs and coordinately downregulate mRNAs involved in biologically significant pathways.

journal_name

Cancer Res

journal_title

Cancer research

authors

Palmer RD,Murray MJ,Saini HK,van Dongen S,Abreu-Goodger C,Muralidhar B,Pett MR,Thornton CM,Nicholson JC,Enright AJ,Coleman N,Children's Cancer and Leukaemia Group.

doi

10.1158/0008-5472.CAN-09-3301

subject

Has Abstract

pub_date

2010-04-01 00:00:00

pages

2911-23

issue

7

eissn

0008-5472

issn

1538-7445

pii

0008-5472.CAN-09-3301

journal_volume

70

pub_type

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