The testicular germ cell tumour genome.
Human testicular germ cell tumour (TGCT) of adolescents and young adults develop from precursor lesions called carcinoma in situ (CIS), which is believed to originate from diploid primordial germ cells during foetal life. CIS is initiated by an aneuploidisation event accompanied by extensive chromosome instability. The further transformation of CIS into invasive TGCT (seminomas and nonseminomas) is associated with increased copy number of chromosome arm 12p, most often seen as isochromosome 12p. Despite the morphological distinctions between seminomatous and nonseminomatous TGCTs, they have many of the same regional genomic disruptions, although frequencies may vary. However, the two histological subtypes have quite distinct epigenomes, which is further evident from their different gene expression patterns. CIS develops from cells with erased parental imprinting, and the seminoma genome is under-methylated compared to that of the nonseminoma genome. High throughput microarray technologies have already pinpointed several genes important to TGCT, and will further unravel secrets of how specific genes and pathways are regulated and deregulated throughout the different stages of TGCT tumourigenesis. In addition to acquiring new insights into the molecular mechanisms of TGCT development, understanding the TGCT genome will also provide clues to the genetics of human embryonic development and of chemotherapy response, as TGCT is a good model system to both.
Skotheim
Rolf I
RI
Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, N-0310 Oslo, Norway.
Lothe
Ragnhild A
RA
D002278:Carcinoma in Situ / Q000235:genetics; D015870:Gene Expression; D016161:Genes, Retinoblastoma; D011905:Genes, ras; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D023281:Genomics; D018237:Germinoma / Q000235:genetics*; D006801:Humans; D008297:Male; D013736:Testicular Neoplasms / Q000235:genetics*