Lanterna Rally

Author: Mansoureh Akouchekian

Publisher: Cuvillier Verlag

Published: 2008-10-07

Total Pages: 92

ISBN-13: 3736927592

The appearance of mtDNA abnormalities including deletions, duplications, insertions or combinations of them in colorectal cancer (CRC) patients was investigated in this work. Our result showed that 11 of 90 CRC patients had a 8.7 kb mtDNA deletion (12.2%) while this deletion was not found in 33 healthy controls. (P=0.035) We conclude that the 8.7 kb deletion can be a secondary effect of the cancer process, which is not inherited. This is the first report on large scale deletions in CRC. We also analyzed the correlation between cancers and mitochondrial haplogroups. The relationship between CRC and each of 9 major mitochondrial haplogroups were examined in Iranian CRC patients. This is the first study to trace mtDNA HVSI variants in CRC patients of the Persian population. Our data showed that patients with CRC have a significantly (P=0.001) higher frequency of haplogroup K (9.5%) when compared with controls (0%). The mitochondrial polymorphisms in haplogroup K might play a causative role in predisposing to CRC. Variations in the D-loop region were found in both CRC patients and healthy people but the frequency of SNPs in CRC patients was higher than in control samples. We found 13 new polymorphisms that had not been recorded in the mitochondrial database. We also detected one T→C transition at np16519 in 28 out of 40 patients (70%). In a recent study researchers reported that the T16519C variation worsen the outcome of pancreatic cancer patients, possibly because it is involved in altering cellular metabolism. Because we found this mutation frequently in our healthy controls (43%) and could not find any differentiation among our patients with respect to the alleles at this mutation, we conclude that the functional significance of this mutation needs further investigation. We also analyzed somatic mutations in mitochondrial genes encoding subunits of the respiratory complex I. Seven somatic mutations in the MT-ND1 gene were found. Six of these mutations were synonymous mutations. The T4216C mutation that was detected in 26% of the CRC tested samples resulted in the substitution of tyrosine with the amino acid histidine at amino acid position 304. The T4216C mutation was recently reported in LHON patients (Povalko et al., 2005). The patients in our study who carried the T4216C mutation had no known vision problems. It is difficult to speculate about the role of this mutation in CRC. LHON mutations were shown to affect complex I in mitochondria and other investigators found other mutations in different parts of this gene. To show pathogenicity of this mutation or find its role in cancer, more investigations particularly in mtDNA of LHON patients are needed. Because cancer is a multifactorial disease and a causative mutation which leads to blindness and cancer has not been reported, we conclude that this mutation may be a secondary effect or rare polymorphism.