Korean J Gynecol Oncol Colposc.  2000 Mar;11(1):3-12.

The Identification of Genetic Alteration in Cervical Cancer by Comparative Genomic Hybridization (CGH)

• Kim YT
• Lee SB
• Jee KJ
• Kim JH
• Kim YM
• Mok JE
• Nam JH

Abstract

Until recently, cytogenetic studies failed to identify any landmark chromosomal aberrations associated with cervical carcinomas, Recent comparative genome hybridization(CGH) studies have, however, demonstrated that one of the most consistent chromosomal abnormality that marks the transition of carcinoma in situ (CIS) of the cervix to invasive carcinoma is the gain of specific chromosome 3q sequences. Although HPV infection has been demonstrated to be a most important initiating event in the development of most cervical cancers, other additional genetic events are also required for eventual development or progression of invasive cancer. The genetic alterations in cervical cancer were investigated by CGH method using fh frozen specimens. CGH is based on two-color in situ hybridization where genomic tumor DNA is labeled with fluorochrome (FITC) and a normal reference genome is labeled with fluorochrome (Rhodamine) by nick translation. Following co-hybridization of the deferentially labeled genomes to normal reference metaphase chromosomes, Computer Assisted Image Analyzer interprets multicolor fluorescence. The volumetric change in the dual color is typically detected as gain or loss of the DNA sequences in specific region of chromosome. In this study, the pattern of chromosomal aberrations in cervical cancer was not similar to that reported previously by other authors. Overall chromosomal aberration was observed in 46.2%(12/26 cases). The gain of chromosome 5, 11q, 15q, and 17q was most frequent. In deletion, 1q loss was most frequent. There was some cell to cell variability of CGH results in a same tumor sample. The results await careful interpretation and there are several possible reasons of such difference. First reason is a possibility of racial difference in the pattern of chromosomal alteration necessary for cervical carcinogenesis and second one is a possibility of faulty analysis by either improper standardization of computer software or heterogeneity of specimen due to normal cell contamination. However, from the finding that there was no chromosomal aberration in all myometria used for normal control, threshold of normal fluorescence profile in our CGH seems to be reliable. The genetic studies on cervical cancer by this CGH technique should provide new insights into the molecular pathogenesis of lower genital tract cancer and allow for more logical and targeted approach to the cervical cancer management.

MeSH Terms

Base Sequence
Carcinogenesis
Carcinoma in Situ
Cervix Uteri
Chromosome Aberrations
Chromosomes, Human, Pair 5
Comparative Genomic Hybridization*
Cytogenetics
DNA
Female
Fluorescence
Genome
In Situ Hybridization
Logic
Metaphase
Population Characteristics
Uterine Cervical Neoplasms*
DNA