Frequent somatic mutations of mitochondrial DNA in esophageal squamous cell carcinoma - PubMed (original) (raw)
Comparative Study
. 2004 Jan 10;108(2):228-31.
doi: 10.1002/ijc.11564.
Affiliations
- PMID: 14639607
- DOI: 10.1002/ijc.11564
Comparative Study
Frequent somatic mutations of mitochondrial DNA in esophageal squamous cell carcinoma
Hiroshi Kumimoto et al. Int J Cancer. 2004.
Abstract
Recent studies of various cancers, such as those of the breast, head and neck, bladder and lung, reported that 46-64% of somatic mutations in the D-loop region of mitochondrial DNA (mtDNA) are observed. However, in esophageal cancer, only a low rate (5%) of somatic mutations has so far been reported in one article (Hibi, K. et al., Int J Cancer 2001;92:319-321). Thus, to confirm this we analyzed the somatic mutations for hypervariable regions (HVR-I and HVR-II) in the D-loop of mtDNA to reevaluate the possibility of mitochondrial genetic instability in this cancer. We amplified both HVRs by PCR and DNA samples obtained from 38 esophageal tumors and matched normal tissues, and then sequenced them. Comparing the sequences of tumors to those of normal tissues, we found 14 somatic mutations in 13 patients (34.2%). Eleven mutations were at the C consecutive stretch from position 303 to 309 of MITOMAP in the mitochondria databank (http://www.mitomap.org/), 1 at position 215 in HVR-II and 2 at positions 16,304 and 16,324 in HVR-I. There were 41 types of germ line variations in HVR-I including 2 not so far recorded in the mtDNA databank and 17 in HVR-II including 1 not yet recorded. We also determined nuclear genome instability of these 38 specimens by analyzing 3 independent microsatellite sequences. While 4 specimens showed a single microsatellite change, which is tumor specific, we did not find any co-relation between a somatic mtDNA mutation and microsatellite instability of nuclear genome DNA. These results suggest that mtDNA mutations might show a genetic instability in esophageal cancer independently from a nuclear genome instability.
Copyright 2003 Wiley-Liss, Inc.
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