Comparative genomic hybridization analysis of chromosomal alterations induced by the development of resistance to thymidylate synthase inhibitors.
نویسندگان
چکیده
Acquired resistance to chemotherapy is a major obstacle to the successful treatment of cancer. In the past, technical limitations prevented the detection of genetic alterations associated with such resistance on a genome-wide scale. This study evaluated comparative genomic hybridization (CGH) as a tool to detect candidate regions of the genome associated with chemoresistance. Using a variation of conventional CGH, DNA from cell lines that were resistant to thymidylate synthase inhibitors (raltitrexed and 5-fluorouracil) and their sensitive parent cells were evaluated. In MCF-7 and H630 cells that were resistant to raltitrexed, only a single region of change (18p gain) was apparent. The third cell line, H630R10, which was resistant to 5-fluorouracil, had changes in several genomic regions following the acquisition of resistance, including 18p gain. Gain in the chromosomal region containing the thymidylate synthase gene (18p11.32) was detected by CGH in all three resistant cell lines. However, additional novel regions of interest were identified in the cells that were resistant to 5-fluorouracil. These results suggest that CGH is of potential use in the detection of regions of the genome involved in chemoresistance.
منابع مشابه
Comparative Genomic Hybridization Analysis of Chromosomal Alterations Induced by the Development of Resistance to Thymidylate Synthase Inhibitors1
Acquired resistance to chemotherapy is a major obstacle to the successful treatment of cancer. In the past, technical limitations pre vented the detection of genetic alterations associated with such resist ance on a genome-wide scale. This study evaluated comparative genomic hybridization (CGH) as a tool to detect candidate regions of the genome associated with chemoresistance. Using a variatio...
متن کاملI-37: Genome Instability and DNA Damage in Male Somatic and Germ Cells Expressed as Chromosomal Microdeletion and Aneuploidy Is A Major Cause of Male Infertility
Background: Sperm chromatin insufficiencies leading to low sperm count and quality, infertility and transmission of chromosomal microdeletion and aneuploidies to next generations can be due to exposure to environmental pollutions, chemicals and natural or manmade ionizing radiation. In this project which has continued for more than 10 years and is unique in many technical aspects in Iran and in...
متن کاملComprehensive multiplatform biomarker analysis of 199 anal squamous cell carcinomas.
Anal squamous cell carcinoma (ASCC) is a rare, HPV-associated malignancy typically diagnosed in early stages and definitively treated with chemoradiation. In situations where patients exhibit metastatic or recurrent disease, treatment options are severely limited. In this study, molecular alterations were identified that could be used to aid in therapeutic decisions for patients with metastatic...
متن کاملMolecular Dissection Using Array Comparative Genomic Hybridization and Clinical Evaluation of An Infertile Male Carrier of An Unbalanced Y;21 Translocation: A Case Report and Review of The Literature
Chromosomal defects are relatively frequent in infertile men however, translocations between the Y chromosome and autosomes are rare and less than 40 cases of Y-autosome translocation have been reported. In particular, only three individuals has been described with a Y;21 translocation, up to now. We report on an additional case of an infertile man in whom a Y;21 translocation was associated wi...
متن کاملAssociation of Chromosomal Alterations with Arsenite-Induced Tumorigenicity of Human HaCaT Keratinocytes in Nude Mice
Inorganic arsenic is a well-documented human carcinogen. Chronic low-dose exposure to inorganic arsenic is associated with an increased incidence of a variety of cancers, including skin, lung, bladder, and liver cancer. Because genetic alterations often occur during cancer development, the objective of this study was to explore what types of genetic alterations were induced by chronic exposure ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Cancer research
دوره 58 22 شماره
صفحات -
تاریخ انتشار 1998