Cyclin D1 abnormalities and tobacco exposure in head and neck squamous cell carcinoma.
BACKGROUND
Amplification of the cyclin D1 (CCND1) gene, which encodes a cell cycle regulating protein, has been described in several solid tumors including head and neck squamous cell carcinoma (HNSCC). While correlations between CCND1 amplification and tumor behavior have been suggested, no investigation has focused on risk factor exposure as a potential cause of CCND1 alteration.


METHODS
Southern blotting was used to identify CCND1 amplification in 57 previously untreated HNSCC tumor specimens Tissue from 27 cases was analyzed for CCND1 mRNA expression by Northern biot analysis.


RESULTS
In 13/57 (23%) cases, a 2-5 fold amplification of CCND1 was found. CCND1 mRNA expression was higher in amplified than in non-amplified tumors and supported an association between CCND1 amplification and increased expression of CCND1 mRNA. No correlation was found between CCND1 amplification or CCND1 expression and clinical or pathological parameters. However, analysis of risk factor exposure revealed that patients with greater tobacco exposure were more likely to have tumors with CCND1 amplification (p = .037). Also, tobacco exposure was correlated with CCND1 expression in tumors.


CONCLUSIONS
Tobacco exposure is a well-known risk factor for HNSCC. CCND1 amplification and alterations in expression may be causally related to tobacco carcinogen exposure and lead to a loss of cell cycle regulation.
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
B J
BJ
Davidson
W M
WM
Lydiatt
M P
MP
Abate
S P
SP
Schantz
R S
RS
Chaganti
D000368:Aged; D015152:Blotting, Northern; D015139:Blotting, Southern; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D019938:Cyclin D1; D016213:Cyclins / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D015870:Gene Expression; D006258:Head and Neck Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015513:Oncogene Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*
D016213:Cyclins; D015513:Oncogene Proteins; D012333:RNA, Messenger; D019938:Cyclin D1