Abstract
In search of tumor-specific mitochondrial DNA (mtDNA) mutations in head and neck squamous cell cancer, we found heteroplasmy in the blood of two individuals, i.e., these individuals carried two alleles of mtDNA. In both cases, the tumor was found to be homoplasmic, i.e., it contained only one of the two mtDNA alleles present in blood. More interestingly, in one case the tumor had acquired the wild-type allele, while in the other case it contained the mutant allele only. Sequencing of the whole 16.5 kb mtDNA showed that the observed heteroplasmic positions in the D-loop region, nucleotides 152 and 16187, respectively, were the only differences between tumor and blood mtDNA genotypes in these individuals. Our findings thus strongly support the hypothesis that accumulation of mtDNA mutations in solid tumors occurs by clonal and random expansion of pre-existing alleles and is not necessary for the metabolic changes generally associated with tumor formation, the Warburg effect.
References
Sep 13, 1993·Biochimica Et Biophysica Acta·C Van den BogertJ W Taanman
May 1, 1997·Electrophoresis·A AlonsoM Sancho
Mar 17, 2000·Science·M S FlissD Sidransky
Aug 31, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·S Eva SingletaryFrederick L Greene
Jan 15, 2003·Experimental Physiology·Patricio Fernández-SilvaJulio Montoya
Jan 15, 2003·Experimental Physiology·Jürgen-Christoph von Kleist-RetzowWolfram S Kunz
Jan 23, 2003·Proceedings of the National Academy of Sciences of the United States of America·Jin ZhangGiuseppe Attardi
Feb 24, 1956·Science·O WARBURG
Oct 23, 2003·Nature Reviews. Cancer·Mukesh VermaSudhir Srivastava
Nov 4, 2004·Trends in Genetics : TIG·Robert McFarlandDouglass M Turnbull
Dec 14, 2004·Journal of Medical Genetics·G ZsurkaW S Kunz
Sep 29, 2005·PLoS Medicine·Antonio SalasHans-Jürgen Bandelt
Dec 31, 2005·Nucleic Acids Research·Max Ingman, Ulf Gyllensten
Aug 8, 2006·Oncogene·M BrandonD C Wallace
Aug 8, 2006·Oncogene·A ChatterjeeD Sidransky
Oct 31, 2006·Oral Oncology·Simon Florian PreussOrlando Guntinas-Lichius
Jan 20, 2007·American Journal of Human Genetics·Gábor ZsurkaWolfram S Kunz
Apr 26, 2007·Proceedings of the National Academy of Sciences of the United States of America·Shaoyu ZhouJoseph A Califano
Oct 5, 2007·Nucleic Acids Research·Kim J KrishnanDoug Turnbull
Jan 29, 2008·Nature Genetics·Lynsey M CreePatrick F Chinnery
Jan 30, 2008·Nature Genetics·Konstantin Khrapko
Apr 5, 2008·Science·Kaori IshikawaJun-Ichi Hayashi
Citations
May 13, 2010·The International Journal of Biochemistry & Cell Biology·Katarína SmolkováPetr Ježek
Mar 13, 2012·The Journal of Pathology·Nicholas A Wright
Jun 15, 2010·Environmental and Molecular Mutagenesis·Mariola KulawiecJason H Bielas
May 2, 2013·Head & Neck·Lucio MontebugnoliMaria Pia Foschini
Mar 5, 2019·PloS One·Kaori IshikawaKazuto Nakada
Oct 6, 2010·Virchows Archiv : an International Journal of Pathology·Andrea Ambrosini-SpaltroVincenzo Eusebi
Apr 20, 2018·Mitochondrial DNA. Part A. DNA Mapping, Sequencing, and Analysis·Annica HedbergSteinar D Johansen
Oct 10, 2015·Oncotarget·Christian U HuebbersRudolf J Wiesner
Apr 8, 2020·Carcinogenesis·Sophie HaumannRudolf J Wiesner