ALLELIC LOSS IN SQUAMOUS-CELL CARCINOMAS OF THE LARYNX - DISCORDANCE BETWEEN PRIMARY AND METASTATIC TUMORS

The mutational inactivation of suppressor genes, a process required fo r cancer progression, generates new genetic subclones within a tumor. The allelic losses that frequently unmask these mutations serve not on ly as markers of the chromosomal locations of these genes but also as clonal fingerprints of the shifting relationships between these geneti cally heterogeneous cell populations. The rise of the metastasis-compe tent subclone to dominance within the primary tumor should be reflecte d in the similarity of the genetic fingerprints of the primary tumor a nd its resultant metastases. We have tested this hypothesis by compari ng the patterns of allelic loss of individual primary laryngeal squamo us cell carcinomas and their resultant cervical lymph node metastases at 16 different genetically polymorphic loci on 15 chromosome arms. Al though primary tumors and metastases both frequently lose heterozygosi ty on the same chromosome arms (3p, 9p, 9q, 13q, and 17p), five of the 12 metastases differed from their primary tumors at one or two of the loci examined. Discordance between the two tumor cell populations fro m the same patient is suggestive of either subclone heterogeneity with in the primary tumor at the time of establishment of the metastasis or further clonal evolution of both tumors after metastasis. (C) 1995 Wi ley-Liss, Inc.