title: Novel mitochondrial mutations in the ATP6 and ATP8 genes in patients with breast cancer.
abstract: The role of the mitochondria in the process of carcinogenesis, mainly oxidative phosphorylation, mostly concerns their participation in the production of free radicals and ATP and in the process of apoptosis. The purpose of this study was to detect potential changes in the genes encoding the subunits 6 and 8 of the ATP synthase and their impact on the enzyme's biochemical properties, structure and function in patients with breast tumors. The tested material was mitochondrial DNA (mtDNA) isolated from specimens of ductal carcinoma (carcinoma ductale) Tp1-2Np0-1Mp0, blood and non-cancerous tissue of mammary gland (control), sampled from 50 patients who had been operated for breast cancer. In the case of missense-type changes in the mtDNA, protein prediction software was used to assess their effect on the biochemical properties of the protein, its structure and function. We identified 8 changes in the ATP6 gene in 36/50 examined breast cancer cell samples and 5 changes in the ATP8 gene (10/50). Most of them were homoplasmic changes of missense type. Four of the changes (A8439C, G8858C, C9130G and T9119G) had not been described in the literature before. The identified mutations and polymorphisms, especially those of missense type, can affect mitochondrial functions, especially if the conservative domain of the protein is concerned. Replacement of 'wild-type' mtDNA by mutated mtDNA can be an important event in carcinogenesis.
authors.affiliation: Department of Oncology, Medical University of Lublin, 20-090 Lublin, Poland.
authors.forename: Ludmiła
authors.initials: L
authors.lastname: Grzybowska-Szatkowska
authors.affiliation: Department of Biological Bases of Animal Production, University of Life Sciences in Lublin, 20-950 Lublin, Poland.
authors.forename: Brygida
authors.initials: B
authors.lastname: Slaska
authors.affiliation: Department of Biology and Genetics, Medical University of Lublin, 20-093 Lublin, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Rzymowska
authors.affiliation: Department of Oncology, Medical University of Lublin, 20-090 Lublin, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Brzozowska
authors.affiliation: Department of Clinical Dietetics, Medical University of Lublin, 20-093 Lublin, Poland.
authors.forename: Bolesław
authors.initials: B
authors.lastname: Floriańczyk
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology*; D004272:DNA, Mitochondrial / Q000235:genetics; D030562:Databases, Protein; D005260:Female; D006801:Humans; D042361:Mammary Glands, Human / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics*; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics*; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
chemical_list: D004272:DNA, Mitochondrial; C501005:MT-ATP6 protein, human; C513300:MT-ATP8 protein, human; D025261:Mitochondrial Proton-Translocating ATPases
references.citation: Nucleic Acids Res. 2009 Jan;37(Database issue):D323-7
references.pmid: 18971256
references.citation: Mitochondrial DNA. 2012 Apr;23(2):106-11
references.pmid: 22397379
references.citation: Int J Cancer. 2012 Jul 1;131(1):158-64
references.pmid: 21826645
references.citation: Breast Cancer Res Treat. 2010 Jun;121(2):511-8
references.pmid: 19266278
references.citation: Cancer Res. 2001 Feb 15;61(4):1299-304
references.pmid: 11245424
references.citation: Cancer Res. 2001 Aug 15;61(16):5998-6001
references.pmid: 11507041
references.citation: Philos Trans R Soc Lond B Biol Sci. 2013 Jun 10;368(1622):20120267
references.pmid: 23754818
references.citation: Proc Int Conf Intell Syst Mol Biol. 1998;6:175-82
references.pmid: 9783223
references.citation: J Mol Biol. 1982 May 5;157(1):105-32
references.pmid: 7108955
references.citation: Mol Med Rep. 2012 Nov;6(5):923-30
references.pmid: 22895648
references.citation: Mitochondrial DNA. 2014 Jun;25(3):238-43
references.pmid: 23656294
references.citation: J Carcinog. 2007 Jan 26;6:1
references.pmid: 17257433
references.citation: Carcinogenesis. 2005 Jan;26(1):145-52
references.pmid: 15375011
references.citation: Proc Natl Acad Sci U S A. 2005 Jan 18;102(3):719-24
references.pmid: 15647368
references.citation: Cancer Res. 2005 Sep 1;65(17):8028-33
references.pmid: 16140977
references.citation: Cancer Genet Cytogenet. 2008 Feb;181(1):16-9
references.pmid: 18262047
references.citation: Oncogene. 2006 Aug 7;25(34):4647-62
references.pmid: 16892079
references.citation: J Aging Res. 2011 Feb 15;2011:136435
references.pmid: 21403887
references.citation: Exp Mol Pathol. 2013 Feb;94(1):285-8
references.pmid: 22542792
references.citation: Nucleic Acids Res. 2010 Jan;38(Database issue):D211-22
references.pmid: 19920124
references.citation: J Biol Chem. 2004 Sep 24;279(39):40670-6
references.pmid: 15292229
references.citation: Oncogene. 1998 Oct 15;17(15):1931-7
references.pmid: 9788436
references.citation: Hum Mutat. 2003 Aug;22(2):173-4
references.pmid: 12872259
references.citation: Mitochondrial DNA. 2015 Jun;26(3):452-8
references.pmid: 24102599
references.citation: Bioinformatics. 2003 Jan;19(1):163-4
references.pmid: 12499312
references.citation: Genome Res. 2003 Sep;13(9):2129-41
references.pmid: 12952881
references.citation: Biol Chem. 1999 Jul-Aug;380(7-8):871-7
references.pmid: 10494836
references.citation: Nat Struct Biol. 1994 Jun;1(6):399-409
references.pmid: 7664054