Centromeric breakage as a major cause of cytogenetic abnormalities in oral 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 aberrations with multiple numerical and structural changes in all tumors. Recurrent breakpoints were located at chromosomal bands 1p13 (five tumors), 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 chromosome arms 3q, 5p, 7p, and 8q. As many as 134 of a total of 218 chromosomal breakpoints (61%) occurred in centromeric regions, often resulting in isochromosomes and unbalanced whole-arm translocations. Using fluorescence in situ hybridization with chromosome-specific centromeric alphoid repeat probes, two whole-arm translocations, der(Xq;11q) and a der(3q;11q), 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.
Hermsen
M A
MA
Department of Human Genetics, Free University, Amsterdam, Netherlands.
Joenje
H
H
Arwert
F
F
Welters
M J
MJ
Braakhuis
B J
BJ
Bagnay
M
M
Westerveld
A
A
Slater
R
R
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002503:Centromere; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D002872:Chromosome Deletion; D025063:Chromosome Disorders; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D051379:Mice; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000235:genetics*