title: Genome-wide gene expression profiling of testicular carcinoma in situ progression into overt tumours.
abstract: The carcinoma in situ (CIS) cell is the common precursor of nearly all testicular germ cell tumours (TGCT). In a previous study, we examined the gene expression profile of CIS cells and found many features common to embryonic stem cells indicating that initiation of neoplastic transformation into CIS occurs early during foetal life. Progression into an overt tumour, however, typically first happens after puberty, where CIS cells transform into either a seminoma (SEM) or a nonseminoma (N-SEM). Here, we have compared the genome-wide gene expression of CIS cells to that of testicular SEM and a sample containing a mixture of N-SEM components, and analyse the data together with the previously published data on CIS. Genes showing expression in the SEM or N-SEM were selected, in order to identify gene expression markers associated with the progression of CIS cells. The identified markers were verified by reverse transcriptase-polymerase chain reaction and in situ hybridisation in a range of different TGCT samples. Verification showed some interpatient variation, but combined analysis of a range of the identified markers may discriminate TGCT samples as SEMs or N-SEMs. Of particular interest, we found that both DNMT3B (DNA (cytosine-5-)-methyltransferase 3 beta) and DNMT3L (DNA (cytosine-5-)-methyltransferase 3 like) were overexpressed in the N-SEMs, indicating the epigenetic differences between N-SEMs and classical SEM.
authors.affiliation: University Department of Growth and Reproduction, Rigshospitalet, Section GR-5064, Blegdamsvej 9, Copenhagen DK-2100, Denmark. kristian@almstrup.net
authors.forename: K
authors.initials: K
authors.lastname: Almstrup
authors.forename: C E
authors.initials: CE
authors.lastname: Hoei-Hansen
authors.forename: J E
authors.initials: JE
authors.lastname: Nielsen
authors.forename: U
authors.initials: U
authors.lastname: Wirkner
authors.forename: W
authors.initials: W
authors.lastname: Ansorge
authors.forename: N E
authors.initials: NE
authors.lastname: Skakkebaek
authors.forename: E
authors.initials: E
authors.lastname: Rajpert-De Meyts
authors.forename: H
authors.initials: H
authors.lastname: Leffers
mesh_terms: D002278:Carcinoma in Situ / Q000235:genetics* / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000096:biosynthesis / Q000235:genetics; D020869:Gene Expression Profiling; D016678:Genome; D018237:Germinoma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011627:Puberty; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018239:Seminoma / Q000235:genetics* / Q000473:pathology*; D013736:Testicular Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: C412484:DNMT3L protein, human; D004248:DNA (Cytosine-5-)-Methyltransferases