Mitochondrial mutations in early stage prostate cancer and bodily fluids

Abstract

We recently demonstrated the existence of speci®c patterns of somatic mitochondrial DNA (mtDNA) mutations in several cancers. Here we sought to identify the presence of mtDNA mutations in prostate cancer and their paired PIN lesions. The D-loop region, 16S rRNA, and the NADH subunits of complex I were sequenced to identify mtDNA mutations in 16 matched PIN lesions and primary prostate cancers. Twenty mtDNA mutations were detected in the tumor tissue of three patients. Identical mutations were also identi®ed in the PIN lesion from one patient. This patient with multiple point mutations also harbored a high frequency of microsatellite instability (MSI-H) in nuclear mononucleotide repeat markers. Remarkably, identical mutations were also detected in all (3/3) matched urine and plasma samples obtained from these patients. Although mitochondrial mutations are less common in prostate adenocarcinoma, they occur early in cancer progression and they can be detected in bodily¯uids of early stage disease patients. The identi®cation of MtDNA mutations may complement other early detection approaches for prostate cancer. Oncogene (2001) 20, 5195 ± 5198.

Clinicopathological significance of mitochondrial D-Loop mutations in head and neck carcinoma

“…These data suggest that D-Loop mutations could be considered as a cancer biomarker that may be useful for the early detection of HNSCC. It is all the more important since mtDNA mutations were reported to be easily detectable in bodily fluids and serum of cancer patients (Fliss et al, 2000;Hibi et al, 2001a;Jeronimo et al, 2001;Parrella et al, 2001;Nomoto et al, 2002). As a consequence, it would be interesting to search for D-Loop mutations in saliva and serum of a large series of HNSCC patients in order to evaluate their relevance in association with other tumour-specific molecular alterations in the screening of this cancer in alcohol and tobacco consumers.…”

Mitochondrial mutations in cancer

“…However, thyroid tumors had a relatively low frequency of control region mutants, particularly in the hypervariable homopolymeric C region between nt 303 and 315 (Tong et al, 2003). Ovarian tumors harbored both control region (3/15) and coding region variants in 60% (6/10) of cases (Liu et al, 2001), breast cancer samples contained control region and coding region mutations in 61% (11/18) of samples (Parrella et al, 2001) and prostate cancer tumors had somatic control region mutations in 88% of cases (14/16) (Chen et al, 2002(Chen et al, , 2003 and control region and coding region mutations in 19% (3/16) of cases (Jeronimo et al, 2001). The functional relevance of tumor-specific polypeptide gene missense mutations was demonstrated by three heteroplasmic COI mutations reported in prostate tumors: G5949 (G16X, Stop), T6124C (M74T, CI ¼ 95%) and C6924T (A341S, CI ¼ 100%) (Petros et al, 2005).…”

High frequency of mitochondrial genome instability in human endometrial carcinomas

“…The occurrence of somatic mitochondrial DNA (mtDNA) mutations in various human cancers has recently been reported (Polyak et al, 1998;Fliss et al, 2000;Jeronimo et al, 2001;Jones et al, 2001;Kirches et al, 2001;Maximo et al, 2001;Parrella et al, 2001). The genetic changes include deletions, point mutations and mitochondrial microsatellite instability (mtMSI), defined as the change in length in short base-repetitive sequences of mtDNA.…”