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Malignant and nonmalignant brain tissues differ in their messenger RNA expression patterns for ERCC1 and ERCC2
M D Dabholkar1, M S Berger, J A Vionnet
1Medical Ovarian Cancer Section, National Cancer Institute, Bethesda, Maryland 20892.
Cancer Research
|March 15, 1995
Summary
Disruptions in DNA repair gene expression, specifically ERCC1 and ERCC2, are linked to human malignancies. Nonmalignant tissues show coordinated gene expression, while cancerous tissues exhibit discordant DNA repair pathways.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- DNA repair gene perturbations are implicated in human diseases, including cancers and central nervous system disorders.
- Subtle abnormalities in DNA repair competency may contribute to the transformation of nonmalignant cells into malignant ones.
Purpose of the Study:
- To investigate the association between DNA repair gene expression and human malignancy.
- To compare mRNA expression levels and splicing of ERCC1, ERCC2, and XPAC in malignant and nonmalignant brain tissues.
Main Methods:
- Assayed mRNA expression levels of human DNA repair genes ERCC1, ERCC2, and XPAC in 19 individuals' brain tissues.
- Analyzed differential splicing of the ERCC1 transcript.
- Utilized linear regression to compare gene expression concordance within and between malignant and nonmalignant tissues.
Main Results:
- Nonmalignant tissues demonstrated orderly concordance of ERCC1, ERCC2, and XPAC expression.
- Malignant tissues showed disrupted concordance between ERCC1 and ERCC2, impacting excision and helicase functions.
- Discordance for ERCC1 and ERCC2 was observed between malignant and nonmalignant tissues within individuals, while XPAC concordance was preserved.
Conclusions:
- Disruption of the coordinated relationship between DNA repair gene functions, specifically ERCC1 and ERCC2, may be a molecular hallmark of human malignancy.
- These findings highlight the role of nucleotide excision repair pathway dysregulation in cancer development.