Abstract
BackgroundCarcinoma of uterine cervix is the second most common cancers among women worldwide. Combined radiation and chemotherapy is the choice of treatment for advanced stages of the disease. The prognosis is poor, with a five-year survival rate ranging from about 20–65%, depending on stage of the disease. Therefore, genetic characterization is essential for understanding the biology and clinical heterogeneity in cervical cancer (CC).MethodsWe used a genome-wide screening method – comparative genomic hybridization (CGH) to identify DNA copy number changes in 77 patients with cervical cancer. We applied categorical and survival analyses to analyze whether chromosomal changes were related to clinico-pathologic characteristics and patients survival.ResultsThe CGH analysis revealed a loss of 2q33-q37 (57.1%), gain of 3q (54.5%) and chromosomal amplifications (20.77%) as frequent genetic changes. A total of 15 amplified chromosomal sites were detected in 16 cases that include 1p31, 2q32, 7q22, 8q21.2-q24, 9p22, 10q21, 10q24, 11q13, 11q21, 12q15, 14q12, 17p11.2, 17q22, 18p11.2, and 19q13.1. Recurrent amplified sites were noted at 11q13, 11q21, and 19q13.1. The genomic alterations were further evaluated for prognostic significance in CC patients, and we did not find any correlation with a number of clinical or histological parameters. The tumors harboring HPV18 exhibited higher genomic instability compared to tumors with HPV 16.ConclusionsThis study demonstrated that 2q33-q37 deletions, 3q gains and chromosomal amplifications as characteristic changes in invasive CC. These genetic alterations will aid in the identification of novel tumor suppressor gene(s) at 2q33-q37 and oncogenes at amplified chromosomal sites. Molecular characterization of these chromosomal changes utilizing the current genomic technologies will provide new insights into the biology and clinical behavior of CC.
Highlights
Carcinoma of uterine cervix is the second most common cancers among women worldwide
A number of comparative genomic hybridization (CGH) studies have identified chromosomal changes involving loss of 2q, 3p, 4p, 4q, 5q, 6q, 11q, 13q and 18q regions and gain of 1q, 3q, 5p and 8q at various stages of CC [7,8,9,10,11,12,13,14]. All these studies have commonly identified 3q gain, which occurred at severe dysplasia/carcinoma-in-situ leading to a suggestion that this genetic aberration plays a pivotal role in the transition from dysplasia to invasive CC [7]
Genomic DNA from 77 primary cervical carcinomas was subjected to CGH to identify chromosomal copy number changes
Summary
Carcinoma of uterine cervix is the second most common cancers among women worldwide. Combined radiation and chemotherapy is the choice of treatment for advanced stages of the disease. A number of molecular genetic studies have been attempted to define the genetic alterations and found frequent LOH at 3p, 4p, 4q, 5p, 6p, 6q, 11q and 17p chromosomal regions suggesting the presence of putative tumor suppressor genes on these chromosomes [4,15,16,17,18,19] Despite this cytogenetic and molecular characterization of cervical precancerous and cancerous lesions, the genetic basis of CC development and progression remains poorly understood
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