Identification and functional prediction of mitochondrial complex III and IV mutations associated with glioblastoma

Neuro-oncology
Rhiannon E LloydJohn E McGeehan

Abstract

Glioblastoma (GBM) is the most common primary brain tumor in adults, with a dismal prognosis. Treatment is hampered by GBM's unique biology, including differential cell response to therapy. Although several mitochondrial abnormalities have been identified, how mitochondrial DNA (mtDNA) mutations contribute to GBM biology and therapeutic response remains poorly described. We sought to determine the spectrum of functional complex III and IV mtDNA mutations in GBM. The complete mitochondrial genomes of 10 GBM cell lines were obtained using next-generation sequencing and combined with another set obtained from 32 GBM tissues. Three-dimensional structural mapping and analysis of all the nonsynonymous mutations identified in complex III and IV proteins was then performed to investigate functional importance. Over 200 mutations were identified in the mtDNAs, including a significant proportion with very low mutational loads. Twenty-five were nonsynonymous mutations in complex III and IV, 9 of which were predicted to be functional and affect mitochondrial respiratory chain activity. Most of the functional candidates were GBM specific and not found in the general population, and 2 were present in the germ-line. Patient-specific maps reve...Continue Reading

References

Jan 1, 1995·Journal of Neuro-oncology·C M DirvenD N Louis
Jul 1, 1993·Annals of Neurology·J Poulton, K Morten
Jul 31, 2001·International Journal of Cancer. Journal International Du Cancer·E KirchesK Dietzmann
Jun 5, 2003·The Journal of Biological Chemistry·Hildur PalsdottirCarola Hunte
Sep 10, 2004·Briefings in Functional Genomics & Proteomics·Ilenia D'ErricoCecilia Saccone
Jun 18, 2005·BMC Bioinformatics·Shuhei KinoshitaLawrence Hunter
Aug 4, 2005·Journal of Neuro-oncology·Luisa MontaniniGaetano Finocchiaro
Dec 21, 2007·FEMS Yeast Research·Nick Fisher, Brigitte Meunier
Sep 6, 2008·Nature·UNKNOWN Cancer Genome Atlas Research Network
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Jun 2, 2009·Cancer Genetics and Cytogenetics·Maria LuethPablo Hernáiz Driever
Feb 12, 2010·Journal of Pediatric Hematology/oncology·Maria LuethPablo Hernáiz Driever
Apr 24, 2010·Molecular Neurobiology·Bartlomiej B OrdysIan R Whittle
Jul 6, 2010·Nucleic Acids Research·Kai WangHakon Hakonarson
Jul 6, 2011·Nucleic Acids Research·Boris RevaChris Sander
Sep 13, 2011·The EMBO Journal·Thorsten AlthoffWerner Kühlbrandt
Dec 6, 2011·Nucleic Acids Research·Francesco RubinoMarcella Attimonelli
Dec 6, 2011·Surgical Neurology International·Ifeoma UgonaboAftab Karim
Mar 27, 2012·Briefings in Bioinformatics·Iain MilneDavid Marshall
Jun 1, 2012·Nucleic Acids Research·Mingkun LiMark Stoneking
Aug 15, 2012·Proceedings of the National Academy of Sciences of the United States of America·Tatianna C LarmanJ G Seidman
Sep 21, 2012·BMC Genomics·Rhiannon E LloydD Timothy J Littlewood
Sep 25, 2012·Nature Reviews. Cancer·Douglas C Wallace
Nov 16, 2012·Nature·Scott B Vafai, Vamsi K Mootha
Jan 8, 2013·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Siegal SadetzkiUNKNOWN Gliogene Consortium
Apr 18, 2013·PloS One·Corinne E GriguerClaudia R Oliva
Sep 21, 2013·Neuro-oncology·Robert DubrowJoseph T King
Oct 15, 2013·Cell·Cameron W BrennanUNKNOWN TCGA Research Network
Apr 15, 2014·Journal of Neuro-oncology·Ruth F DeightonJames McCulloch
Apr 20, 2014·World Journal of Gastroenterology : WJG·Hsin-Chen LeeChin-Wen Chi
May 21, 2014·Neuro-oncology·Quinn T OstromJill S Barnholtz-Sloan

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Citations

Jul 4, 2019·Scientific Reports·Erik FasteriusCristina Al-Khalili Szigyarto
May 12, 2017·Frontiers in Cell and Developmental Biology·Marie Strickland, Elizabeth A Stoll
Jul 18, 2017·Mitochondrial DNA. Part A. DNA Mapping, Sequencing, and Analysis·Rhiannon E McGeehanQian An
Jul 13, 2019·Mitochondrion·Rajnish Kumar SinghRameshwar N K Bamezai
Mar 7, 2021·Mitochondrion·María Del Mar GonzálezMaria Pilar Aluja
Jan 30, 2018·Biochimica Et Biophysica Acta. Reviews on Cancer·Catherine J LibbyAnita B Hjelmeland
Nov 24, 2020·The European Journal of Neuroscience·Angeliki-Maria VlaikouMichaela D Filiou
Jun 3, 2021·International Journal of Molecular Sciences·Mariceli Baia Leão BarrosBárbara do Nascimento Borges
Dec 8, 2021·Personalized Medicine·Bee Hong SoonRahman Jamal

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Methods Mentioned

BETA
PCR

Software Mentioned

Statistica
Statsoft
ANNOVAR
GATK Unified Genotyper

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