Genome-wide gene expression profiling of testicular carcinoma in situ progression into overt tumours

• Published in: British journal of cancer Vol. 92; no. 10; pp. 1934 - 1941
• Main Authors: ALMSTRUP, K, HOEI-HANSEN, C. E, NIELSEN, J. E, WIRKNER, U, ANSORGE, W, SKAKKEBAEK, N. E, RAJPERT-DE MEYTS, E, LEFFERS, H
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 23.05.2005
• Subjects: Biological and medical sciences; Cancer research; Carcinoma in Situ - genetics; Carcinoma in Situ - pathology; Cell Transformation, Neoplastic - genetics; DNA (Cytosine-5-)-Methyltransferases - biosynthesis; DNA (Cytosine-5-)-Methyltransferases - genetics; Gene expression; Gene Expression Profiling; Genetics and Genomics; Genome; Genomes; Germinoma - genetics; Germinoma - pathology; Gynecology. Andrology. Obstetrics; Humans; In Situ Hybridization; Male; Male genital diseases; Medical research; Medical sciences; Oligonucleotide Array Sequence Analysis; Polymerase chain reaction; Puberty; Reverse Transcriptase Polymerase Chain Reaction; Seminoma - genetics; Seminoma - pathology; Stem cells; Testicular Neoplasms - genetics; Testicular Neoplasms - pathology; Tumors; Carcinoma in situ; Malignant tumor; Gene expression; nonseminoma; Male genital system; Gene expression profile; testicular cancer; Seminoma; DNMT3L; Cancerology; Tumor progression; Genome; Male genital diseases; Testicular diseases; Testicle cancer
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6602560

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.