Mitochondrial DNA mutations in normal and tumor tissues from breast cancer patients

Abstract

We have characterized the mtDNA in normal and breast cancer tissues from seven patients. Both types of tissue showed point mutation heteroplasmies and extensive deletions of the mtDNA. The analysis of these polymorphisms allowed us to infer the mtDNA composition of the breast cell that underwent malignant transformation.

Quantitative analysis of mitochondrial DNA 4977-bp deletion in sporadic breast cancer and benign breast diseases

“…The mtDNA 4977 mutation was first reported as occurring in one out of seven breast cancer samples (7). Later, three studies reported a different pattern of mtDNA 4977 mutation in tumors compared to normal tissue.…”

“…The mtDNA 4977 mutation may contribute to respiratory defects in many types of human malignancy such as colorectal, liver, lung, and prostate cancers, and may be associated with tumor progression. To date, only few studies have evaluated the association between the mtDNA 4977 mutation and breast cancer risk, and the findings from these studies have been inconsistent (4,(7)(8)(9). The inconsistency in previous studies may be due, in part, to the use of non-quantitative detection methods and/or failure in quantitative PCR strategies to identify, and disqualify from use, pairs of primers which will also efficiently co-amplify nuclear DNA.…”

Mitochondrial mutations in cancer

“…Numerous mtDNA mutations have now been reported in cancer (Chinnery et al, 2002;Copeland et al, 2002). Early studies of cancer cell mtDNAs reported dimeric mtDNAs in human leukemia leukocytes (Clayton et al, 1970), partial deletions in the mtDNA tRNA Tyr and tRNA Trp genes in rat liver tumor mtDNAs (Taira et al, 1983), and heteroplasmy based on restriction digests of tumor mtDNAs (Bianchi et al, 1995). However, the first clear demonstration that a mtDNA mutation in cancer cells could be functionally significant came from the report of a renal adenocarcinoma in which 50% of the mtDNAs contained a 294 nt in-frame deletion in the mtDNA ND1 gene resulting in a truncated mRNA (Horton et al, 1996).…”

Somatic mitochondrial DNA (mtDNA) mutations in papillary thyroid carcinomas and differential mtDNA sequence variants in cases with thyroid tumours

“…A small number of studies have demonstrated somatic mutations in colorectal and gastric carcinomas (Alonso et al, 1997;Burgart et al, 1995;Polyak et al, 1998). However, most studies which have focused on breast, thyroid and renal neoplasms have been limited by small sample sizes and insensitive or incomplete screening techniques and have found con¯icting results (Bianchi et al, 1995;Ebner et al, 1991;Horton et al, 1996;Johnson et al, 1996;Muller-Hocker et al, 1998;Tallini et al, 1994;Welter et al, 1989).…”