Facile Detection of Mitochondrial DNA Mutations in Tumors and Bodily Fluids-Reference-Cited by-同舟云学术

Facile Detection of Mitochondrial DNA Mutations in Tumors and Bodily Fluids

Published:2000-03-17 Issue:5460 Volume:287 Page:2017-2019
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Fliss Makiko S.¹,Usadel Henning¹,Caballero Otávia L.¹,Wu Li¹,Buta Martin R.¹,Eleff Scott M.²,Jen Jin¹,Sidransky David¹

Affiliation:

1. Department of Otolaryngology–Head and Neck Surgery, Head and Neck Cancer Research Division,

2. Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Abstract

Examination of human bladder, head and neck, and lung primary tumors revealed a high frequency of mitochondrial DNA (mtDNA) mutations. The majority of these somatic mutations were homoplasmic in nature, indicating that the mutant mtDNA became dominant in tumor cells. The mutated mtDNA was readily detectable in paired bodily fluids from each type of cancer and was 19 to 220 times as abundant as mutated nuclear p53 DNA. By virtue of their clonal nature and high copy number, mitochondrial mutations may provide a powerful molecular marker for noninvasive detection of cancer.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference25 articles.

1. Mammalian mitochondrial genetics: heredity, heteroplasmy and disease

2. MITOMAP: A Human Mitochondrial Genome Database Center for Molecular Medicine Emory University Atlanta GA (www.gen.emory.edu/mitomap.html).

3. Repair of Oxidative Damage to Nuclear and Mitochondrial DNA in Mammalian Cells

4. Somatic mutations of the mitochondrial genome in human colorectal tumours

5. Paired normal and tumor specimens along with blood and bodily fluids were collected after surgical resections with prior consent from patients in the Johns Hopkins University Hospital. Tumor specimens were frozen and microdissected on a cryostat so that the tumor samples contained greater than 70% neoplastic cells. DNA from tumor sections was digested with 1% SDS/Proteinase K extracted by phenol-chloroform and ethanol precipitated. Control DNAs from peripheral lymphocytes matched normal tissues urine saliva and BAL fluid were processed in the same manner as described in (12).

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