Clonal cytogenetic evolution in a squamous cell carcinoma of the skin from a xeroderma pigmentosum patient

Cytogenetic changes in epithelial neoplasms are often complex, making it difficult to determine which are the primary abnormalities and which are secondary. In this report, we describe clonal evolution in a cytogenetically simple, but clinically aggressive squamous cell cancer of the skin from a patient with xeroderma pigmentosum. Chromosome preparations were analyzed from a direct harvest, three independent primary harvests, and passaged cell lines. Three closely related tumor subclones were identified in the primary cultures, and all three proliferated in vitro. Monosomy 4 and a chromosome 9 rearrangement were present in all three subclones and monosomy 21 was present in two subclones. An i(9p) and an i(9q) were derived from the same chromosome 9, and there was concurrent loss of the homologous chromosome 9. In addition, each subclone was characterized by a further specific evolutionary change: t(5;7) (q11.2;p22) in subclone 1, der (11)t(10;11) (q21;p14) in subclone 2, and der (14)t(13;14) (q14;q32) in subclone 3. All three subclones were represented by hypodiploid and hypotetraploid metaphases. Loss of chromosomes from hypotetraploid cells and an 11q+ were the only other changes found in this tumor. The early genetic events in the evolution of this squamous cell cancer, monosomy 4, i(9p), i(9q), and monosomy 21, represent loss of chromosome regions that are commonly lost in other squamous cell carcinomas of the head and neck region. Taken together, these observations indicate that genes on these chromosomal regions are probably important and possibly sufficient for the development of squamous cell carcinoma.