Chromosomal translocations involving 11q13 contribute to cyclin D1 overexpression in squamous cell carcinoma of the head and neck.
CCND1 amplification results in cyclin D1 overexpression. However, other unidentified genetic mechanisms contribute to enhanced gene expression. In the present study, 32 squamous cell carcinoma of the head and neck (SCCHN) were investigated regarding chromosomal abnormalities involving 11q13 by cytogenetic analysis, genomic CCND1 amplification by differential PCR and FISH, and cyclin D1 expression on the mRNA and protein level by differential RT-PCR and immunohistochemistry, respectively. CCND1 amplification, observed in 11 of 32 (34%) tumours, resulted in overexpression of cyclin D1 on the mRNA and/or protein level, in 3 cases in association with chromosomal translocations. In cytogenetic analysis, 4 tumours had hsr(11)(q13), all of which showed CCND1 amplification and cyclin D1 overexpression. Overexpression of cyclin D1 was detected at the mRNA level in 23 tumours (72%) and on the protein level in 25 tumours (78%). In one case a translocation was seen together with cyclin D1 overexpression on the mRNA level, without any cytogenetic or molecular signs of amplification. Furthermore, cases with cyclin D1 overexpression were frequently observed in the absence of any genomic rearrangement. We conclude that, besides amplifications, chromosomal translocations and other transcriptional or translational regulatory mechanisms are involved in CCND1 deregulation.
Akervall
Jan
J
Department of Otorhinolaryngology/Head and Neck Surgery, University Hospital, SE-221 85 Lund, Sweden.
Borg
Ake
A
Dictor
Michael
M
Jin
Charlotte
C
Jin
Yuesheng
Y
Tanner
Minna
M
Isola
Jorma
J
Mertens
Fredrik
F
Wennerberg
Johan
J
D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D016612:Paraffin Embedding; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D019938:Cyclin D1