title: Somatic alterations in mitochondrial DNA and mitochondrial dysfunction in gastric cancer progression.
abstract: Energy metabolism reprogramming was recently identified as one of the cancer hallmarks. One of the underlying mechanisms of energy metabolism reprogramming is mitochondrial dysfunction caused by mutations in nuclear genes or mitochondrial DNA (mtDNA). In the past decades, several types of somatic mtDNA alterations have been identified in gastric cancer. However, the role of these mtDNA alterations in gastric cancer progression remains unclear. In this review, we summarize recently identified somatic mtDNA alterations in gastric cancers as well as the relationship between these alterations and the clinicopathological features of gastric cancer. The causative factors and potential roles of the somatic mtDNA alterations in cancer progression are also discussed. We suggest that point mutations and mtDNA copy number decreases are the two most common mtDNA alterations that result in mitochondrial dysfunction in gastric cancers. The two primary mutation types (transition mutations and mononucleotide or dinucleotide repeat instability) imply potential causative factors. Mitochondrial dysfunction-generated reactive oxygen species may be involved in the malignant changes of gastric cancer. The search for strategies to prevent mtDNA alterations and inhibit the mitochondrial retrograde signaling will benefit the development of novel treatments for gastric cancer and other malignancies.
authors.affiliation: Hsin-Chen Lee, Chin-Wen Chi, Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Hsin-Chen
authors.initials: HC
authors.lastname: Lee
authors.affiliation: Hsin-Chen Lee, Chin-Wen Chi, Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Kuo-Hung
authors.initials: KH
authors.lastname: Huang
authors.affiliation: Hsin-Chen Lee, Chin-Wen Chi, Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Tien-Shun
authors.initials: TS
authors.lastname: Yeh
authors.affiliation: Hsin-Chen Lee, Chin-Wen Chi, Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Chin-Wen
authors.initials: CW
authors.lastname: Chi
mesh_terms: D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000235:genetics*; D018450:Disease Progression; D006801:Humans; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology*; D009154:Mutation; D017354:Point Mutation; D017382:Reactive Oxygen Species; D015398:Signal Transduction; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species
keywords: Gastric cancer; Mitochondrial dysfunction; Somatic mitochondrial DNA mutations
references.citation: Nucleic Acids Res. 2002 Jul 1;30(13):2817-24
references.pmid: 12087165
references.citation: Annu Rev Genet. 2006;40:159-85
references.pmid: 16771627
references.citation: Br J Cancer. 2006 Jan 30;94(2):268-74
references.pmid: 16404428
references.citation: Neurology. 1995 Apr;45(4):762-8
references.pmid: 7723967
references.citation: Free Radic Biol Med. 2002 May 1;32(9):804-12
references.pmid: 11978482
references.citation: EMBO J. 2005 Oct 5;24(19):3482-92
references.pmid: 16163384
references.citation: Mol Cell Biol. 1995 Feb;15(2):964-74
references.pmid: 7823960
references.citation: Mutat Res. 2004 Mar 22;547(1-2):71-8
references.pmid: 15013701
references.citation: Mutagenesis. 2004 May;19(3):169-85
references.pmid: 15123782
references.citation: FEBS Lett. 1994 Oct 31;354(1):79-83
references.pmid: 7957906
references.citation: Leukemia. 2003 Dec;17(12):2487-91
references.pmid: 14523470
references.citation: Cancer Res. 2005 Mar 1;65(5):1655-63
references.pmid: 15753359
references.citation: Mitochondrion. 2010 Mar;10(2):174-82
references.pmid: 20006738
references.citation: Cell. 2011 Mar 4;144(5):646-74
references.pmid: 21376230
references.citation: Oncol Rep. 2003 Nov-Dec;10(6):1837-41
references.pmid: 14534705
references.citation: J Alzheimers Dis. 2009;18(2):345-53
references.pmid: 19584455
references.citation: Proc Natl Acad Sci U S A. 2007 May 22;104(21):9001-6
references.pmid: 17517629
references.citation: Science. 2008 May 2;320(5876):661-4
references.pmid: 18388260
references.citation: Eur J Cancer. 1999 Feb;35(2):316-9
references.pmid: 10448277
references.citation: Br J Cancer. 2004 Jun 14;90(12):2390-6
references.pmid: 15150555
references.citation: Mutat Res. 1999 Jul 15;443(1-2):37-52
references.pmid: 10415430
references.citation: BMC Cancer. 2006 Apr 18;6:93
references.pmid: 16620376
references.citation: J Gastroenterol Hepatol. 2005 Nov;20(11):1679-84
references.pmid: 16246185
references.citation: Am J Pathol. 1995 Oct;147(4):1105-11
references.pmid: 7573355
references.citation: Mitochondrion. 2007 Sep;7(5):347-53
references.pmid: 17707697
references.citation: Cancer Res. 2001 Feb 15;61(4):1299-304
references.pmid: 11245424
references.citation: World J Surg. 2007 Jan;31(1):51-9
references.pmid: 17171498
references.citation: Cancer Res. 2001 Aug 15;61(16):5998-6001
references.pmid: 11507041
references.citation: Nat Rev Genet. 2012 Dec;13(12):878-90
references.pmid: 23154810
references.citation: J Clin Invest. 2013 Apr;123(4):1405-12
references.pmid: 23543062
references.citation: Cancer Res. 2001 Oct 15;61(20):7623-6
references.pmid: 11606403
references.citation: Ageing Res Rev. 2010 Nov;9 Suppl 1:S47-58
references.pmid: 20816876
references.citation: Biochem Biophys Res Commun. 2014 Jan 3;443(1):156-60
references.pmid: 24287180
references.citation: Nat Genet. 1998 Nov;20(3):291-3
references.pmid: 9806551
references.citation: Ann N Y Acad Sci. 2004 Apr;1011:310-6
references.pmid: 15126307
references.citation: Int J Mol Sci. 2009 Feb;10(2):674-701
references.pmid: 19333428
references.citation: Cancer Res. 2002 Feb 15;62(4):972-6
references.pmid: 11861366
references.citation: Genes Chromosomes Cancer. 2002 Nov;35(3):256-60
references.pmid: 12353267
references.citation: Cancer Cell. 2010 Jan 19;17(1):41-52
references.pmid: 20129246
references.citation: Mol Cell Biochem. 2012 Nov;370(1-2):69-78
references.pmid: 22821176
references.citation: Mol Cell. 2004 Apr 9;14(1):1-15
references.pmid: 15068799
references.citation: Mutat Res. 1998 May 25;400(1-2):99-115
references.pmid: 9685598
references.citation: World J Gastroenterol. 2003 Sep;9(9):1925-9
references.pmid: 12970877
references.citation: J Hum Genet. 2009 Sep;54(9):516-24
references.pmid: 19629138
references.citation: Genet Mol Res. 2004 Sep 30;3(3):395-409
references.pmid: 15614730
references.citation: Oncol Lett. 2013 Oct;6(4):1098-1102
references.pmid: 24137470
references.citation: BMC Endocr Disord. 2007 Oct 04;7:8
references.pmid: 17916247
references.citation: Genes Chromosomes Cancer. 2006 Jul;45(7):629-38
references.pmid: 16568452
references.citation: Carcinogenesis. 2006 Mar;27(3):409-18
references.pmid: 16221732
references.citation: Am J Hum Genet. 1994 Oct;55(4):760-76
references.pmid: 7942855
references.citation: Arch Med Res. 2006 Aug;37(6):730-5
references.pmid: 16824932
references.citation: Carcinogenesis. 2005 Jan;26(1):145-52
references.pmid: 15375011
references.citation: Toxicology. 2003 Nov 15;193(1-2):3-34
references.pmid: 14599765
references.citation: Hum Mol Genet. 2008 Apr 1;17(7):986-95
references.pmid: 18156159
references.citation: Electrophoresis. 1997 May;18(5):682-5
references.pmid: 9194590
references.citation: Pharmacol Ther. 2013 Mar;137(3):318-30
references.pmid: 23159371
references.citation: PLoS One. 2013 Jun 14;8(6):e65578
references.pmid: 23799027
references.citation: Mutagenesis. 2008 Mar;23(2):137-42
references.pmid: 18252697
references.citation: Cancer Res. 2003 Jul 15;63(14):3866-71
references.pmid: 12873974
references.citation: Biochim Biophys Acta. 2012 Jul;1820(7):1102-10
references.pmid: 22561002
references.citation: Clin Cancer Res. 2009 May 1;15(9):2995-3002
references.pmid: 19383819
references.citation: Med Oncol. 2013 Jun;30(2):552
references.pmid: 23550275
references.citation: Mech Ageing Dev. 2013 Oct;134(10):460-6
references.pmid: 24012633
references.citation: J Biol Chem. 2006 Nov 24;281(47):36241-8
references.pmid: 17005553
references.citation: Hum Mol Genet. 2009 May 1;18(9):1578-89
references.pmid: 19208652
references.citation: Proc Natl Acad Sci U S A. 2005 Jan 18;102(3):719-24
references.pmid: 15647368
references.citation: J Med Genet. 2004 May;41(5):e65
references.pmid: 15121793
references.citation: Oncogene. 2006 Aug 7;25(34):4768-76
references.pmid: 16892089
references.citation: Ann N Y Acad Sci. 2005 May;1042:109-22
references.pmid: 15965052
references.citation: J Pathol. 2003 Feb;199(2):237-42
references.pmid: 12533837
references.citation: Gene. 2005 Jul 18;354:132-9
references.pmid: 15978749
references.citation: Mutat Res. 2004 Sep;567(1):1-61
references.pmid: 15341901
references.citation: Clin Chim Acta. 2007 May;381(1):50-5
references.pmid: 17397816
references.citation: Science. 2005 Jul 15;309(5733):481-4
references.pmid: 16020738
references.citation: Genes Chromosomes Cancer. 2011 Oct;50(10):800-11
references.pmid: 21748819
references.citation: Biochim Biophys Acta. 2010 Aug;1806(1):58-65
references.pmid: 20122996
references.citation: Genes Chromosomes Cancer. 2005 Sep;44(1):19-28
references.pmid: 15892105
references.citation: FEBS J. 2009 Oct;276(20):5768-87
references.pmid: 19796285
references.citation: EMBO J. 2001 Apr 17;20(8):1910-20
references.pmid: 11296224
references.citation: J Bioenerg Biomembr. 2007 Jun;39(3):267-74
references.pmid: 17551814
references.citation: World J Surg. 2014 Apr;38(4):910-7
references.pmid: 24322174
references.citation: Biochim Biophys Acta. 2010 Mar;1800(3):264-70
references.pmid: 19527772
references.citation: Hum Mol Genet. 2010 Mar 15;19(6):1019-32
references.pmid: 20028790
references.citation: Lancet Oncol. 2006 Apr;7(4):309-15
references.pmid: 16574546
references.citation: World J Gastroenterol. 2005 Jun 7;11(21):3304-6
references.pmid: 15929189
references.citation: Oncogene. 2002 Nov 7;21(51):7839-49
references.pmid: 12420221
references.citation: Science. 2000 Mar 17;287(5460):2017-9
references.pmid: 10720328
references.citation: Int J Mol Med. 2003 Aug;12(2):169-74
references.pmid: 12851712
references.citation: Int J Colorectal Dis. 2008 Dec;23(12):1223-32
references.pmid: 18769884
references.citation: Nature. 2004 May 27;429(6990):417-23
references.pmid: 15164064
references.citation: Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1838-43
references.pmid: 12578990
references.citation: Int J Cancer. 2005 Oct 10;116(6):920-4
references.pmid: 15856456
references.citation: Nat Genet. 1993 May;4(1):67-71
references.pmid: 8513327
references.citation: Nat Rev Cancer. 2012 Oct;12(10):685-98
references.pmid: 23001348
references.citation: World J Gastroenterol. 2013 Dec 21;19(47):8880-6
references.pmid: 24379611
references.citation: Science. 1956 Feb 24;123(3191):309-14
references.pmid: 13298683