CENTROMERIC BREAKAGE AS A MAJOR CAUSE OF CYTOGENETIC ABNORMALITIES INORAL SQUAMOUS-CELL CARCINOMA

Cytogenetic analysis of short-term explant tumor cultures derived from 11 human oral squamous cell carcinomas (nine from primary tumors and two from nude mouse xenograft cultures) revealed clonal chromosomal ab errations with multiple numerical and structural changes in all tumors . Recurrent breakpoints were located at chromosomal bands 1p13 (five t umors), 11q13 (four tumors), 3q27-29 (three tumors), and 12q13 (three tumors). Four tumors had a homogeneously staining region at band 11q13 . Consistent chromosomal losses included 3p, 9p13-pter, and 18q22-qter , each occurring in eight tumors. Gain of material was observed for ch romosome arms 3q, 5p, 7p, and 8q. As many as 134 of a total of 218 chr omosomal breakpoints (61%) occurred in centromeric regions, often resu lting in isochromosomes and unbalanced whole-arm translocations. Using fluorescence in situ hybridization with chromosome-specific centromer ic alphoid repeat probes, two whole-arm translocations, der(Xq;11q) an d a der(3q;11q), each from a different tumor, were shown to contain ju xtaposed centromeric sequences of both participating chromosomes, stro ngly suggesting that the breakpoints were within the centromeres. We p ropose that centromeric breakage is an important mechanism for the gen eration of genetic imbalance in the development of oral squamous cell carcinoma. (C) 1996 Wiley-Liss, Inc.