Centromeric breakage as a major cause of cytogenetic abnormalities in oral squamous cell carcinoma

✍ Scribed by Mario A. J. A. Hermsen; Hans Joenje; Fré Arwert; Marij J. P. Welters; Boudewijn J. M. Braakhuis; Marjan Bagnay; Andries Westerveld; Rosalyn Slater

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 719 KB
• Volume: 15
• Category: Article
• ISSN: 1045-2257
• DOI: 10.1002/(sici)1098-2264(199601)15:1<1::aid-gcc1>3.0.co;2-8

✦ Synopsis

Cytogenetic analysis of short-term explant tumor cultures derived from I I human oral squamous cell carcinomas (nine from primary tumors and two from nude mouse xenograft cultures) revealed clonal chromosomal aberrations with multiple numerical and structural changes in all tumors. Recurrent breakpoints were located at chromosomal bands I p I 3 (five tumors), I I q I 3 (four tumors), 3q27-29 (three tumors), and I2q I 3 (three tumors). Four tumors had a homogeneously staining region at band I I q 13. Consistent chromosomal losses included 3p, 9p I 3-pter, and I8q22-qter, each occurring in eight tumors. Gain of material was observed for chromosome arms 3q, 5p, 7p, and 8q. As many as I34 of a total of 21 8 chromosomal breakpoints (6 I %) occurred in centromeric regions, often resulting in isochromosomes and unbalanced whole-arm translocations. Using fluorescence in sku hybridization with chromosome-specific centromeric alphoid repeat probes, two whole-arm translocations, der(Xq; I I q) and a der(3q; I I q), each from a different tumor, were shown to contain juxtaposed centromeric sequences of both participating chromosomes, strongly suggesting that the breakpoints were within the centromeres. We propose that centromeric breakage is an important mechanism for the generation of genetic imbalance in the development of oral squamous cell carcinoma.