Colorectal cancer (CRC) is the third most common diagnosed and cause of cancer related deaths in both men and women in the United States. Numerous studies have analyzed mitochondria DNA mutations in CRC and other tumors. Results from these studies have detected high mutation rates which may lead to mitochondrial deregulation and tumor progression. Most CRCs develop from adenopolyps via the adenoma-carcinoma sequence. Therefore, analysis of mitochondrial mutations and gene expression may provide a mechanism for inhibition of this tumoral sequence in individuals with a high risk of developing CRC. In the present study, PCR based sequencing and reverse transcription-quantitative PCR (RT-qPCR) were used to determine if mutations in mitochondrial encoded genes and levels of expression of these genes could influence the progression of the adenoma- carcinoma tumoral sequence. Genes analyzed included MT-RNR1, MT-COI, MT-ATP6, MT- MT-CYB, and mitochondrial ND genes that are involved in the normal metabolism of mitochondria. Measurements were made for 34 tissue sample pairs obtained from various types of colorectal adenomas and corresponding normal surrounding tissues. Additionally, mitochondrial complexes I (NADH: ubiquinone oxidoreductase) and III (CoQH2-cytochrome c reductase) protein was analyzed. There was progressive differential expression of mt-genes and complexes I and III proteins among the colorectal tumor stages relative to their paired normal samples. The level of complexes I and III were higher in tumor tissues relative to normal surrounding tissues. Noticeably, the expression of MT-COI was higher in late stage carcinomas among; all studied transcripts. We detected 54 point mutations in one region ranging from 11871-11877. The frequency of these mutations in all stages was as followed; 71.5% in tubular adenoma, 57% tubulovillous, and 43% in villous and carcinoma. Our results suggest that alterations in mt-gene expression play a role in the transformation of the colorectal tumoral stages.
Citation Format: LaShanale M. Wallace, Sharifeh Mehrabi, Xuebiao Yao, Felix Aikhionbare. Mitochondrial mutations and gene expression analysis in colorectal adenopolyps. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5163.