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PRAD-1 CYCLIN D1 GENE AMPLIFICATION CORRELATES WITH MESSENGER-RNA OVEREXPRESSION AND TUMOR PROGRESSION IN HUMAN LARYNGEAL CARCINOMAS
Author(s): JARES P, FERNANDEZ PL, CAMPO E, NADAL A, BOSCH F, AIZA G, NAYACH I, TRASERRA J, CARDESA A
Source: CANCER RESEARCH    Volume: 54    Issue: 17    Pages: 4813-4817    Published: SEP 1 1994  
Times Cited: 207     References: 34     
Abstract: PRAD-1 is a putative oncogene localized on chromosome 11q13 which encodes cyclin D1, a novel cyclin involved in cell cycle regulation. Amplification of this gene has recently been reported in several human tumors including breast and head and neck carcinomas. In this study we have analyzed the presence of PRAD-1/cyclin D1 gene amplification and mRNA overexpression in a series of 46 matched normal mucosas and squamous cell carcinomas of the larynx. PRAD-1/cyclin D1 was found to be amplified 2- to 12-fold in 17 carcinomas (37%). DNA amplification correlated with advanced local invasion (P = 0.0015), presence of lymph node metastases (P = 0.0078), and stage IV of the tumors (P = 0.0021). mRNA overexpression was found in 15 of the 43 (35%) cases examined and it was also significantly associated with advanced Local invasion (P = 0.0025) and stage IV carcinomas (P = 0.0032). A significant association was observed between gene amplification and mRNA overexpression (P < 0.0001) with only 3 discordant cases (2 amplifications with no overexpression and 1 overexpressed carcinoma with no gene amplification). Furthermore, the degree of DNA amplification correlated with the levels of mRNA expression (r = 0.6; P = 0.024). These findings suggest that the PRAD-1/cyclin D1 gene may be an important target of 11q13 amplifications in laryngeal carcinomas and the activation of this gene may be involved in the progression of these tumors. Its association with advanced-stage tumors indicates that PRAD-1/cyclin D1 gene amplification and overexpression may be of prognostic significance.
Document Type: Article
Language: English
Addresses:
1. UNIV BARCELONA, HOSP CLIN BARCELONA, DEPT ANAT PATHOL, E-08036 BARCELONA, SPAIN
2. UNIV BARCELONA, HOSP CLIN BARCELONA, POSTGRAD SCH HEMATOL FARRERAS VALENTI, BARCELONA, SPAIN
3. UNIV BARCELONA, HOSP CLIN BARCELONA, DEPT OTOLARYNGOL, BARCELONA, SPAIN
4. UNIV LLEIDA, DEPT BASIC MED SCI, LLEIDA, SPAIN
Publisher: AMER ASSOC CANCER RESEARCH, PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106
Subject Category: Oncology
IDS Number: PD695
ISSN: 0008-5472
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