Less DeltamtDNA4977 than normal in various types of tumors suggests that cancer cells are essentially free of this mutation

Dani, M. A; Dani, S. U; Lima, S. P; Martinez, A; Rossi, B. M; Soares, F; Zago, M. A; Simpson, A. J

Dani, M. A; Dani, S. U; Lima, S. P; Martinez, A; Rossi, B. M; Soares, F; Zago, M. A; Simpson, A. J.

Afiliação

Dani, M. A; University of São Paulo. Medical School. Department of Genetics. Ribeirão Preto. BR
Dani, S. U; Genon Genética. Ribeirão Preto. BR
Lima, S. P; Gene Therapy Center. Ribeirão Preto. BR
Martinez, A; NIH. NCI. Cell and Cancer Biology Branch. US
Rossi, B. M; A.C. Camargo Cancer Hospital. Department of Pelvic Surgery. São Paulo. BR
Soares, F; A.C. Camargo Cancer Hospital. Pathology Division. São Paulo. BR
Zago, M. A; University of São Paulo. Faculty of Medicine. Center for Cell Therapy and Regional Blood Center. Ribeirão Preto. BR
Simpson, A. J; Ludwig Institute for Cancer Research. Laboratory of Cancer Genetics. São Paulo. BR

Genet. mol. res. (Online) ; Genet. mol. res. (Online);3(3): 395-409, 2004. tab, ilus, graf

Article em En | LILACS | ID: lil-482169

Biblioteca responsável: BR1.1

ABSTRACT

ABSTRACT

Levels of mtDNA(4977) deletions (DeltamtDNA(4977)) have been found to be lower in tumors than in adjacent non-tumoral tissues. In 87 cancer patients, DeltamtDNA(4977) was detected by multiplex polymerase chain reaction (PCR) amplification in 43 (49%) of the tumors and in 74 (85%) of the samples of non-tumoral tissues that were adjacent to the tumors. DeltamtDNA(4977) deletions were detected in 24% of the breast tumors, 52% of the colorectal tumors, 79% of the gastric tumors, and 40% of the head and neck tumors as compared with 77, 83, 100, and 90% of the adjacent respective non-tumoral tissues at the same DNA template dilution. Based on limiting dilution PCR of 16 tumors and their adjacent non-tumoral tissues, it was found that the amount of DeltamtDNA(4977) was 10- to 100-fold lower in the tumor than in the respective control non-tumoral tissues. Real-time PCR experiments were performed to quantify the number of DeltamtDNA(4977) deletions per cell, by determining the mitochondrial-to-nuclear DNA ratio. In all of the cases of breast, colorectal, gastric, and head and neck cancer the proportion of DeltamtDNA(4977) in tumors was lower than that of the respective non-tumoral tissue. Traces of DeltamtDNA(4977) in tumors were apparently due to contamination of tumor tissue with surrounding non-tumoral tissue, as evidenced by tumor microdissection and in situ PCR techniques, suggesting that tumors are essentially free of this mutation. Although the metabolic effect of DeltamtDNA(4977) may be minimal in normal (non-tumor) tissue, in tissue under stress, such as in tumors, even low levels of DeltamtDNA(4977) deletions may be intolerable.

Assuntos

Feminino; Humanos; Deleção de Sequência/genética; Mutação/genética; Neoplasias Colorretais/genética; Neoplasias Gástricas/genética; Neoplasias da Mama/genética; Neoplasias de Cabeça e Pescoço/genética; Estudos de Casos e Controles; DNA Mitocondrial/genética; Reação em Cadeia da Polimerase; Células Tumorais Cultivadas

Palavras-chave

Cancer; DmtDNA4977; In situ PCR; Kerns-Sayre syndrome deletion mutation; Mitochondria; Mitochondrial DNA; Real-time PCR

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Texto completo: 1 Coleções: 01-internacional Base de dados: LILACS Assunto principal: Neoplasias Gástricas / Neoplasias da Mama / Neoplasias Colorretais / Deleção de Sequência / Neoplasias de Cabeça e Pescoço / Mutação Tipo de estudo: Observational_studies Limite: Female / Humans Idioma: En Revista: Genet. mol. res. (Online) Assunto da revista: BIOLOGIA MOLECULAR / GENETICA Ano de publicação: 2004 Tipo de documento: Article País de afiliação: Brasil / Estados Unidos País de publicação: Brasil

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