Tissue microarray analysis of cyclin D1 gene amplification and gain in colorectal carcinomas.
Colorectal cancer is one of the most common neoplastic diseases and one of the leading causes of cancer-related deaths. Elevated beta-catenin levels in colorectal cancer result in the binding of beta-catenin to LEF-1 and increased transcriptional activation of the CCND1 gene. Overexpression of cyclin D1 is observed in one third of colorectal tumors. CCND1 amplification is the main cause of protein overexpression in numerous human carcinomas. In colorectal cancer, however, no CCND1 amplification has been reported so far. The aim of this study was to determine the frequency of CCND1 amplifications and gains in a large number of colorectal carcinomas, arranged in a tissue microarray, in order to assess their role in colorectal cancer development. The copy number changes, detected by fluorescence in situ hybridization, were predominantly gains (7.6%) and only rarely amplifications (2.5%). In colorectal cancer, the CCND1 copy number increase was neither associated with the tumor phenotype (stage and grade) nor with the tumor localization (colon, rectum or sigmoid colon). In conclusion, even in a small number of colorectal tumors, CCND1 gene amplification is a possible mechanism for the increase in cyclin D1 oncoprotein.
Toncheva
D
D
Department of Medical Genetics, University Hospital 'Queen Joanna', Medical University of Sofia, Sofia, Bulgaria. dragatoncheva@yahoo.com
Petrova
D
D
Tzenova
V
V
Dimova
I
I
Yankova
R
R
Yordanov
V
V
Damjanov
D
D
Todorov
T
T
Zaharieva
B
B
D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D019938:Cyclin D1 / Q000235:genetics*; D005784:Gene Amplification; D006801:Humans; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D012004:Rectal Neoplasms / Q000235:genetics* / Q000473:pathology
D019938:Cyclin D1