title: Mitochondrial genome instability in colorectal adenoma and adenocarcinoma.
abstract: Mitochondrial dysfunction is regarded as a hallmark of cancer progression. In the current study, we evaluated mitochondrial genome instability and copy number in colorectal cancer using Next Generation Sequencing approach and qPCR, respectively. The results revealed higher levels of heteroplasmy and depletion of the relative mtDNA copy number in colorectal adenocarcinoma. Adenocarcinoma samples also presented an increased number of mutations in nuclear genes encoding proteins which functions are related with mitochondria fusion, fission and localization. Moreover, we found a set of mitochondrial and nuclear genes, which cooperate in the same mitochondrial function simultaneously mutated in adenocarcinoma. In summary, these results support an important role for mitochondrial function and genomic instability in colorectal tumorigenesis.
authors.affiliation: Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.|Center for Cell-Based Therapy (CEPID/FAPESP); National institute of Science and Technology in Stem Cell and Cell Therapy (INCTC/CNPq), Regional Blood Center of Ribeirão Preto, Riberão Preto, Brazil.
authors.forename: Luiza F
authors.initials: LF
authors.lastname: de Araujo
authors.affiliation: Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.|Center for Cell-Based Therapy (CEPID/FAPESP); National institute of Science and Technology in Stem Cell and Cell Therapy (INCTC/CNPq), Regional Blood Center of Ribeirão Preto, Riberão Preto, Brazil.
authors.forename: Aline S
authors.initials: AS
authors.lastname: Fonseca
authors.affiliation: Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.|Center for Cell-Based Therapy (CEPID/FAPESP); National institute of Science and Technology in Stem Cell and Cell Therapy (INCTC/CNPq), Regional Blood Center of Ribeirão Preto, Riberão Preto, Brazil.
authors.forename: Bruna R
authors.initials: BR
authors.lastname: Muys
authors.affiliation: Center for Cell-Based Therapy (CEPID/FAPESP); National institute of Science and Technology in Stem Cell and Cell Therapy (INCTC/CNPq), Regional Blood Center of Ribeirão Preto, Riberão Preto, Brazil.
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Plaça
authors.affiliation: Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.|Center for Cell-Based Therapy (CEPID/FAPESP); National institute of Science and Technology in Stem Cell and Cell Therapy (INCTC/CNPq), Regional Blood Center of Ribeirão Preto, Riberão Preto, Brazil.
authors.forename: Rafaela B L
authors.initials: RB
authors.lastname: Bueno
authors.affiliation: Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.|Center for Cell-Based Therapy (CEPID/FAPESP); National institute of Science and Technology in Stem Cell and Cell Therapy (INCTC/CNPq), Regional Blood Center of Ribeirão Preto, Riberão Preto, Brazil.
authors.forename: Julio C C
authors.initials: JC
authors.lastname: Lorenzi
authors.affiliation: Center for Cell-Based Therapy (CEPID/FAPESP); National institute of Science and Technology in Stem Cell and Cell Therapy (INCTC/CNPq), Regional Blood Center of Ribeirão Preto, Riberão Preto, Brazil.
authors.forename: Anemari R D
authors.initials: AR
authors.lastname: Santos
authors.affiliation: Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.|Center for Cell-Based Therapy (CEPID/FAPESP); National institute of Science and Technology in Stem Cell and Cell Therapy (INCTC/CNPq), Regional Blood Center of Ribeirão Preto, Riberão Preto, Brazil.|Center for Medical Genomics (HCFMRP/USP), Center for Integrative Systems Biology (CISBi - NAP/USP), Ribeirão Preto, Brazil.
authors.forename: Greice A
authors.initials: GA
authors.lastname: Molfetta
authors.affiliation: Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.|Center for Cell-Based Therapy (CEPID/FAPESP); National institute of Science and Technology in Stem Cell and Cell Therapy (INCTC/CNPq), Regional Blood Center of Ribeirão Preto, Riberão Preto, Brazil.|Center for Medical Genomics (HCFMRP/USP), Center for Integrative Systems Biology (CISBi - NAP/USP), Ribeirão Preto, Brazil.
authors.forename: Dalila L
authors.initials: DL
authors.lastname: Zanette
authors.affiliation: Center for Cell-Based Therapy (CEPID/FAPESP); National institute of Science and Technology in Stem Cell and Cell Therapy (INCTC/CNPq), Regional Blood Center of Ribeirão Preto, Riberão Preto, Brazil.|Center for Medical Genomics (HCFMRP/USP), Center for Integrative Systems Biology (CISBi - NAP/USP), Ribeirão Preto, Brazil.
authors.forename: Jorge E S
authors.initials: JE
authors.lastname: Souza
authors.affiliation: Center for Cell-Based Therapy (CEPID/FAPESP); National institute of Science and Technology in Stem Cell and Cell Therapy (INCTC/CNPq), Regional Blood Center of Ribeirão Preto, Riberão Preto, Brazil.|Center for Medical Genomics (HCFMRP/USP), Center for Integrative Systems Biology (CISBi - NAP/USP), Ribeirão Preto, Brazil.|Department of Clinical Analysis, Faculty of Pharmaceutical Science of Araraquara, University of São Paulo State, Araraquara, Brazil.
authors.forename: Valeria
authors.initials: V
authors.lastname: Valente
authors.affiliation: Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. wilsonjr@usp.br.|Center for Cell-Based Therapy (CEPID/FAPESP); National institute of Science and Technology in Stem Cell and Cell Therapy (INCTC/CNPq), Regional Blood Center of Ribeirão Preto, Riberão Preto, Brazil. wilsonjr@usp.br.|Center for Medical Genomics (HCFMRP/USP), Center for Integrative Systems Biology (CISBi - NAP/USP), Ribeirão Preto, Brazil. wilsonjr@usp.br.
authors.forename: Wilson A
authors.initials: WA
authors.lastname: Silva
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D054629:Genome, Mitochondrial; D042822:Genomic Instability; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation
chemical_list: D004272:DNA, Mitochondrial
keywords: Colorectal cancer; Genome instability; Heteroplasmy; Mitochondrial genome