Abstract 2101: Differential mtDNA sequence variants in primary tissues of colorectal adeno-polyps
| Autor: | Yupha Vatcharapijarn, Joyce A. Akwe, Sharifeh Mehrabi, Xuebiao Yao, Felix O. Aikhionbare, Gregory P. Adams |
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| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | Cancer Research. 72:2101-2101 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Introduction: Increasing evidence suggest that mitochondrial alterations involved in cellular signal pathways have been associated with tumorigenesis. Differentially diagnosing progressive stages of colorectal adenomatous polyps is important for therapeutic intervention and surveillance. We hypothesized that Mitochondrial DNA (mtDNA) variants in colorectal adenomatous polyps are stage-specific genetic changes. We aimed to identify the genetic mtDNA mutations present in the early stages of colorectal cancer. Methods: MtDNA sequence variants among the different types of colorectal adenomatous polyps: Tubular, Tubulovillous and Villous adenomatous were analyzed from sixty-four tissue samples (33 tumor 31 matched surrounding normal tissue (NST)) with patients mean age 57.1±7. Two mtDNA regions were screened from each sample with two primer pairs spanning 8282-to-10107 and 11673-to-13950bp comprised of the MT-NC7, MT-TK, MT-ND3, ATPase 6, ATPase 8, COX III, ND3, ND4L, ND4 and ND5 genes. The presence of polymorphisms and other sequence variants of mtDNA were also evaluated using the high-resolution restriction endonucleases and PCR based sequencing. Results: Forty-two variants were observed of which 18 of 42 (42%) were not previously reported in the MITODAT reference database. The distribution of observed mutations included, 31% (13/42) Tubular, 52% (22/42) Tubulovillous, 45% (19/42) Villous, 45% (19/42) colorectal cancer (including FAP and JVP). Notably, unreported germline variant, G8573A, in the ATPase 8 gene region was found in 100% tubulovillous adenomas, but not any other samples. A heteroplasmic variant A11873G, in the MTND4 gene was detected in 67% tubular, 78% tubulovillous, 71% villous and 38% cancer subtypes. Given that mutations in ATPase 8 genes inhibits the production of ATP from ADP, and mutations in MTND4 genes prevent the normal interactions of complex I with ubiquinone, affecting the generation of ATP, these observed variants may influence the early stages of colorectal tumor. Conclusion: Therefore, our findings suggest that certain mtDNA sequence variants may contribute as a framework for further differentiation studies of stages of colorectal adeno-polyps. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2101. doi:1538-7445.AM2012-2101 |
| Databáze: | OpenAIRE |
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