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Chromosomal imbalances in four new uterine cervix carcinoma derived cell lines.

Hidalgo A, Monroy A, Arana RM, Taja L, Vázquez G, Salcedo M - BMC Cancer (2003)

Bottom Line: Analysis of our present findings and previously reported data suggest that gains at 1q31-q32 and 7p13-p14, as well as losses at 6q26-q27 are alterations that might be unique for HPV18 positive cases.These chromosomal regions, as well as regions with high copy number amplifications, coincide with known fragile sites and known HPV integration sites.The general pattern of chromosomal imbalances detected in the cells resembled that found in invasive cervical tumors, suggesting that the cells represent good models for the study of cervical carcinoma.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratorio de Oncología Genómica, Unidad de Investigación Médica en Enfermedades Oncológicas, Hospital de Oncología, Centro Médico Nacional Siglo XXI-IMSS, Mexico. alfhm@yahoo.com

ABSTRACT

Background: Uterine cervix carcinoma is the second most common female malignancy worldwide and a major health problem in Mexico, representing the primary cause of death among the Mexican female population. High risk human papillomavirus (HPV) infection is considered to be the most important risk factor for the development of this tumor and cervical carcinoma derived cell lines are very useful models for the study of viral carcinogenesis. Comparative Genomic Hybridization (CGH) experiments have detected a specific pattern of chromosomal imbalances during cervical cancer progression, indicating chromosomal regions that might contain genes that are important for cervical transformation.

Methods: We performed HPV detection and CGH analysis in order to initiate the genomic characterization of four recently established cervical carcinoma derived cell lines from Mexican patients.

Results: All the cell lines were HPV18 positive. The most prevalent imbalances in the cell lines were gains in chromosomes 1q23-q32, 3q11.2-q13.1, 3q22-q26.1, 5p15.1-p11.2, this alteration present as a high copy number amplification in three of the cell lines, 7p15-p13, 7q21, 7q31, 11q21, and 12q12, and losses in 2q35-qter, 4p16, 6q26-qter, 9q34 and 19q13.2-qter.

Conclusions: Analysis of our present findings and previously reported data suggest that gains at 1q31-q32 and 7p13-p14, as well as losses at 6q26-q27 are alterations that might be unique for HPV18 positive cases. These chromosomal regions, as well as regions with high copy number amplifications, coincide with known fragile sites and known HPV integration sites. The general pattern of chromosomal imbalances detected in the cells resembled that found in invasive cervical tumors, suggesting that the cells represent good models for the study of cervical carcinoma.

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CGH ideograms of the genetic imbalances detected in the cell lines. The lines at the right of the chromosome ideogram represent DNA gains, lines at the left, DNA losses. Thick lines represent high copy number amplifications or multi copy deletions (ratio >1.4 or <0.6). The mark closest to the ideogram represents the cell lines CALO, followed by VIPA, INBL and ROVA.
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Figure 1: CGH ideograms of the genetic imbalances detected in the cell lines. The lines at the right of the chromosome ideogram represent DNA gains, lines at the left, DNA losses. Thick lines represent high copy number amplifications or multi copy deletions (ratio >1.4 or <0.6). The mark closest to the ideogram represents the cell lines CALO, followed by VIPA, INBL and ROVA.

Mentions: HPV DNA was detected in all the cell lines. Sequence analysis identified HPV18 in all the samples. All the cell lines presented chromosomal imbalances. A line summary ideogram of the chromosomal imbalances in the cell lines is presented in Figure 1. A complete description of the imbalances detected in each cell line is presented in Table 1. On the average, 19.5 DNA losses and 20.7 gains were detected in the samples, with an average number of chromosomal aberrations of 40.2 alterations per case, ranging from 52 alterations in VIPA to 19 alterations in INBL. The most prevalent imbalances were gains in chromosomes 1q23-q32, 3q11.2-q13.1, 3q22-q26.1, 5p15.1-p11.2. This alteration is present as a high copy number amplification in three of the cell lines, 7p15-p13, 7q21, 7q31, 11q21, and 12q12, and losses in 2q35-qter, 4p16, 6q26-qter, 9q34 and 19q13.2-qter. Comparison between chromosomal imbalances in these cell lines and those found in cervical tumors; indicate the presence of common genetic alterations, suggesting that they represent their tissue of origin. These common regions include gains in 3q22-q26.2 and 5p, and losses on 2q35-qter, 4q32-qter and 18q. Some of these alterations have been detected in early stages of cervical transformation and are conserved in advanced tumors or have been associated with the presence of metastases and with a worse clinical behavior [6,7,10], making the cells good models for the study of genes involved in the maintenance of the transformed phenotype. Compared with the imbalances previously found on HPV18 positive cases [9], there is coincidence for the DNA gains at 1q31-q32, 3q22-q26.3, 5p14 and 7p13-p14, as well as in DNA losses at 2q33-qter and 6q26-q27. Differences among the cell lines and data from invasive cervical tumors were also found. For example, we did not find deletions of 3p or 11q regions in the cell lines. This situation might be explained by the enrichment or selection of a particular cell clone during the cell line establishment.


Chromosomal imbalances in four new uterine cervix carcinoma derived cell lines.

Hidalgo A, Monroy A, Arana RM, Taja L, Vázquez G, Salcedo M - BMC Cancer (2003)

CGH ideograms of the genetic imbalances detected in the cell lines. The lines at the right of the chromosome ideogram represent DNA gains, lines at the left, DNA losses. Thick lines represent high copy number amplifications or multi copy deletions (ratio >1.4 or <0.6). The mark closest to the ideogram represents the cell lines CALO, followed by VIPA, INBL and ROVA.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC153511&req=5

Figure 1: CGH ideograms of the genetic imbalances detected in the cell lines. The lines at the right of the chromosome ideogram represent DNA gains, lines at the left, DNA losses. Thick lines represent high copy number amplifications or multi copy deletions (ratio >1.4 or <0.6). The mark closest to the ideogram represents the cell lines CALO, followed by VIPA, INBL and ROVA.
Mentions: HPV DNA was detected in all the cell lines. Sequence analysis identified HPV18 in all the samples. All the cell lines presented chromosomal imbalances. A line summary ideogram of the chromosomal imbalances in the cell lines is presented in Figure 1. A complete description of the imbalances detected in each cell line is presented in Table 1. On the average, 19.5 DNA losses and 20.7 gains were detected in the samples, with an average number of chromosomal aberrations of 40.2 alterations per case, ranging from 52 alterations in VIPA to 19 alterations in INBL. The most prevalent imbalances were gains in chromosomes 1q23-q32, 3q11.2-q13.1, 3q22-q26.1, 5p15.1-p11.2. This alteration is present as a high copy number amplification in three of the cell lines, 7p15-p13, 7q21, 7q31, 11q21, and 12q12, and losses in 2q35-qter, 4p16, 6q26-qter, 9q34 and 19q13.2-qter. Comparison between chromosomal imbalances in these cell lines and those found in cervical tumors; indicate the presence of common genetic alterations, suggesting that they represent their tissue of origin. These common regions include gains in 3q22-q26.2 and 5p, and losses on 2q35-qter, 4q32-qter and 18q. Some of these alterations have been detected in early stages of cervical transformation and are conserved in advanced tumors or have been associated with the presence of metastases and with a worse clinical behavior [6,7,10], making the cells good models for the study of genes involved in the maintenance of the transformed phenotype. Compared with the imbalances previously found on HPV18 positive cases [9], there is coincidence for the DNA gains at 1q31-q32, 3q22-q26.3, 5p14 and 7p13-p14, as well as in DNA losses at 2q33-qter and 6q26-q27. Differences among the cell lines and data from invasive cervical tumors were also found. For example, we did not find deletions of 3p or 11q regions in the cell lines. This situation might be explained by the enrichment or selection of a particular cell clone during the cell line establishment.

Bottom Line: Analysis of our present findings and previously reported data suggest that gains at 1q31-q32 and 7p13-p14, as well as losses at 6q26-q27 are alterations that might be unique for HPV18 positive cases.These chromosomal regions, as well as regions with high copy number amplifications, coincide with known fragile sites and known HPV integration sites.The general pattern of chromosomal imbalances detected in the cells resembled that found in invasive cervical tumors, suggesting that the cells represent good models for the study of cervical carcinoma.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratorio de Oncología Genómica, Unidad de Investigación Médica en Enfermedades Oncológicas, Hospital de Oncología, Centro Médico Nacional Siglo XXI-IMSS, Mexico. alfhm@yahoo.com

ABSTRACT

Background: Uterine cervix carcinoma is the second most common female malignancy worldwide and a major health problem in Mexico, representing the primary cause of death among the Mexican female population. High risk human papillomavirus (HPV) infection is considered to be the most important risk factor for the development of this tumor and cervical carcinoma derived cell lines are very useful models for the study of viral carcinogenesis. Comparative Genomic Hybridization (CGH) experiments have detected a specific pattern of chromosomal imbalances during cervical cancer progression, indicating chromosomal regions that might contain genes that are important for cervical transformation.

Methods: We performed HPV detection and CGH analysis in order to initiate the genomic characterization of four recently established cervical carcinoma derived cell lines from Mexican patients.

Results: All the cell lines were HPV18 positive. The most prevalent imbalances in the cell lines were gains in chromosomes 1q23-q32, 3q11.2-q13.1, 3q22-q26.1, 5p15.1-p11.2, this alteration present as a high copy number amplification in three of the cell lines, 7p15-p13, 7q21, 7q31, 11q21, and 12q12, and losses in 2q35-qter, 4p16, 6q26-qter, 9q34 and 19q13.2-qter.

Conclusions: Analysis of our present findings and previously reported data suggest that gains at 1q31-q32 and 7p13-p14, as well as losses at 6q26-q27 are alterations that might be unique for HPV18 positive cases. These chromosomal regions, as well as regions with high copy number amplifications, coincide with known fragile sites and known HPV integration sites. The general pattern of chromosomal imbalances detected in the cells resembled that found in invasive cervical tumors, suggesting that the cells represent good models for the study of cervical carcinoma.

Show MeSH
Related in: MedlinePlus