title: Detection of mitochondrial DNA mutations in primary breast cancer and fine-needle aspirates.
abstract: To determine the frequency and distribution of mitochondrial DNA mutations in breast cancer, 18 primary breast tumors were analyzed by direct sequencing. Twelve somatic mutations not present in matched lymphocytes and normal breast tissues were detected in 11 of the tumors screened (61%). Of these mutations, five (42%) were deletions or insertions in a homopolymeric C-stretch between nucleotides 303-315 (D310) within the D-loop. The remaining seven mutations (58%) were single-base substitutions in the coding (ND1, ND4, ND5, and cytochrome b genes) or noncoding regions (D-loop) of the mitochondrial genome. In three cases (25%), the mutations detected in coding regions led to amino acid substitutions in the protein sequence. We then screened an additional 46 primary breast tumors with a rapid PCR-based assay to identify poly-C alterations in D310, and we found seven more cancers with alterations. Using D310 mutations as clonal marker, we detected identical changes in five of five matched fine-needle aspirates and in four of four metastases-positive lymph nodes. The high frequency of D310 alterations in primary breast cancer combined with the high sensitivity of the PCR-based assays provides a new molecular tool for cancer detection.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Division of Head and Neck Cancer Research, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: P
authors.initials: P
authors.lastname: Parrella
authors.forename: Y
authors.initials: Y
authors.lastname: Xiao
authors.forename: M
authors.initials: M
authors.lastname: Fliss
authors.forename: M
authors.initials: M
authors.lastname: Sanchez-Cespedes
authors.forename: P
authors.initials: P
authors.lastname: Mazzarelli
authors.forename: M
authors.initials: M
authors.lastname: Rinaldi
authors.forename: T
authors.initials: T
authors.lastname: Nicol
authors.forename: E
authors.initials: E
authors.lastname: Gabrielson
authors.forename: C
authors.initials: C
authors.lastname: Cuomo
authors.forename: D
authors.initials: D
authors.lastname: Cohen
authors.forename: S
authors.initials: S
authors.lastname: Pandit
authors.forename: M
authors.initials: M
authors.lastname: Spencer
authors.forename: C
authors.initials: C
authors.lastname: Rabitti
authors.forename: V M
authors.initials: VM
authors.lastname: Fazio
authors.forename: D
authors.initials: D
authors.lastname: Sidransky
mesh_terms: D001707:Biopsy, Needle; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018567:Breast Neoplasms, Male / Q000235:genetics* / Q000473:pathology; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation
chemical_list: D004272:DNA, Mitochondrial; D005819:Genetic Markers