Loss of heterozygosity, differentiation, and clonality in microdissected male germ cell tumours

Testicular germ cell tumours (TGCTs) are heterogeneous neoplasms with diffe rent histological patterns and malignant potential. The aim of this study w as to determine whether the main TGCT subtypes (seminoma, embryonal carcino ma, yolk sac tumour, choriocarcinoma, and mature teratoma) are distinguishe d by their loss of heterozygosity (LOH) patterns and whether LOH typing can help to distinguish between clonal and multifocal development of different components in mixed TGCTs, In 76 tumours analysed for allelic losses at 25 chromosomal loci, different LOH patterns were found in distinct histologic al subtypes. A region around D18S543 frequently lost in yolk sac tumours co uld harbour one or more tumour suppressor genes. In 20 microdissected mixed tumours, losses of identical alleles in different histological components in 11 of 20 cases (over 50 per cent) were found, which is in favour of curr ent histogenetic models of clonal TGCT development. Clonal losses were most often found at D13S317 (6 of 20 tumours), Two classes of allelic losses ma y therefore occur during TGCT development: clonal losses which are involved in early transformational events and others related to TGCT differentiatio n along different lines. Copyright (C) 1999 John Wiley & Sons, Ltd.