Numerical abnormalities of the Cyclin D1 gene locus on chromosome 11q13 in non-melanoma skin cancer.
Deregulation of the cell-cycle G1-restriction point control via abnormalities of Rb-pathway components is a frequent event in the formation of cancer. The aim of this study was to evaluate numerical aberrations of the Cyclin D1 (CCND1, PRAD1, bcl-1) gene locus at chromosome 11q13 in basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) of the skin and to compare it with the Cyclin D1 protein expression. Fluorescence in situ hybridization with DNA-probes specific for the Cyclin D1 gene locus and the centromere of chromosome 11 as well as immunostaining for Cyclin D1 protein was applied on 5 microm serial paraffin sections. Six of the 30 (20%) SCCs showed additional Cyclin D1 gene copies and 2/30 (6.6%) cases had a loss of the Cyclin D1 gene locus in relation to the centromere 11 number. In contrast, only one of the 14 BCCs (7%) showed one additional Cyclin D1 gene copy in relation to the centromere 11 number. None of the BCCs demonstrated aneusomy for chromosome 11 in contrast to SCCs, where it was found in 21/30 (70%) cases. Twenty-six of the 30 (86.6%) cutaneous SCCs and 13/14 (93%) BCCs expressed Cyclin D1 protein. All SCCs and the BCC with additional Cyclin D1 gene copies showed positivity for Cyclin D1 protein. Both SCCs with less Cyclin D1 gene copies than centromere 11 signals showed a weak protein expression. Our findings suggest that numerical abnormalities of the Cyclin D1 gene locus could result in an altered gene-dose effect, possibly leading to an aberrant expression in affected tumor cells. This might result in deregulation of cell cycle control, eventually leading to uncontrolled cell cycle progression.
Utikal
Jochen
J
Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, D-68135 Mannheim, Germany. jochen.utikal@haut.ma.uni-heidelberg.de
Udart
Martin
M
Leiter
Ulrike
U
Kaskel
Peter
P
Peter
Ralf Uwe
RU
Krähn
Gertraud
G
D000368:Aged; D000782:Aneuploidy; D002280:Basal Cell Carcinoma / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D012878:Skin Neoplasms / Q000235:genetics*
D019938:Cyclin D1