Genomic and gene expression signature of the pre-invasive testicular carcinoma in situ.
Testicular cancer is the most common malignancy among men in the reproductive age and the incidence is increasing, probably caused by environmental factors. Most testicular cancers are testicular germ cell tumours and all originate from a carcinoma in situ (CIS) pattern. In this review, we focus on the pre-invasive CIS and its possible fetal origin by reviewing recent data originating from DNA microarrays and comparative genomic hybridisations. A comparison of gene expression and genomic aberrations reveal chromosomal "hot spots" with mutual clustering of gene expression and genomic amplification. Some of the genes found in the hot spots may be involved in creating the CIS phenotype. On the other hand, many genes that are highly expressed in CIS are not present in the hot-spot areas. The gene expression profile of CIS thus most likely reflects the combined result of genomic amplification and increased transcriptional activation and/or deficiency in the epigenetic silencing of specific loci. Amplification of chromosome 12p, appears to be a good genomic marker of the transition from the pre-malignant to malignant CIS cell; this is consistent with recent findings of propagation advantages in cultured undifferentiated embryonic stem cells after spontaneous amplification in similar regions. The gene expression profile of CIS cells has remarkable similarity to that of embryonic stem cells and supports our long-standing hypothesis of an early developmental origin of CIS and testicular germ cell cancer.
Almstrup
Kristian
K
University Department of Growth and Reproduction, Section GR-5064, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. kristian@almstrup.net
Ottesen
Anne Marie
AM
Sonne
Si Brask
SB
Hoei-Hansen
Christina E
CE
Leffers
Henrik
H
Rajpert-De Meyts
Ewa
E
Skakkebaek
Niels E
NE
D002278:Carcinoma in Situ / Q000209:etiology / Q000235:genetics / Q000473:pathology; D002869:Chromosome Aberrations; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016678:Genome; D006801:Humans; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000209:etiology / Q000235:genetics / Q000473:pathology; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D013223:Statistics as Topic; D013736:Testicular Neoplasms / Q000209:etiology / Q000235:genetics / Q000473:pathology