Cancer begins with multiple cumulative epigenetic and genetic alterations that sequencially transform a cell, or a group of cells in a particular organ. The early genetic events might lead to clonal expansion of pre-neoplastic daughter cells in a particular tumor field. Subsequent genomic changes in some of these cells drive them towards the malignant phenotype. These transformed cells are diagnosed histopathologically as cancers owing to changes in cell morphology. Conceivably, a population of daughter cells with early genetic changes (without histopathology) remain in the organ, demonstrating the concept of field cancerization. With present technological advancement, including laser capture microdisection and high-throughput genomic technologies, carefully designed studies using appropriate control tissue will enable identification of important molecular signatures in these genetically transformed but histologically normal cells. Such tumorspecific biomarkers should have excellent clinical utility. This review examines the concept of field cancerization in several cancers and its possible utility in four areas of oncology; risk assessment, early cancer detection, monitoring of tumor progression and definition of tumor margins.
SummaryVirion proteins recognize their cognate nucleic acid for encapsidation into virions through recognition of a specific nucleotide sequence contained within that nucleic acid. Viruses like bacteriophage P22, which have partially circularly permuted, double-stranded virion DNAs, encapsidate DNA through processive series of packaging events in which DNA is recognized for packaging only once at the beginning of the series. Thus a single DNA recognition event programmes the encapsidation of multiple virion chromosomes. The protein product of P22 gene 3 , a terminase component, is thought to be responsible for this recognition. The site on the P22 genome that is recognized by the gene 3 protein to initiate packaging series is called the pac site. We report here a strategy for assaying pac site activity in vivo , and the utilization of this system to identify and characterize the site genetically. It is an asymmetric site that spans 22 basepairs and is located near the centre of P22 gene 3 .
We present mitochondrial haplogroup characterizations of the prehistoric Anasazi of the United States (US) Southwest. These data are part of a long-term project to characterize ancient Great Basin and US Southwest samples for mitochondrial DNA (mtDNA) diversity. Three restriction site polymorphisms (RSPs) and one length polymorphism identify four common Native American matrilines (A, B, C, and D). The Anasazi (n = 27) are shown to have a moderate frequency of haplogroup A (22%), a high frequency of haplogroup B (56%), and a low frequency of C (15%). Haplogroup D has not yet been detected among the Anasazi. In comparison to modern Native American groups from the US Southwest, the Anasazi are shown to have a distribution of haplogroups similar to the frequency pattern exhibited by modern Pueblo groups. A principal component analysis also clusters the Anasazi with some modern (Pueblo) Southwestern populations, and away from other modern (Athapaskan speaking) Southwestern populations. The Anasazi are also shown to have a significantly different distribution of the four haplogroups as compared to the eastern Great Basin Great Salt Lake Fremont (n = 32), although both groups cluster together in a principal component analysis. The context of our data suggests substantial stability within the US Southwest, even in the face of the serious cultural and biological disruption caused by colonization of the region by European settlers. We conclude that although sample numbers are fairly low, ancient DNA (aDNA) data are useful for assessing long-term populational affinities and for discerning regional population structure.
Background: Nuclear mitochondrial pseudogenes (numts) are a potential source of contamination during mitochondrial DNA PCR amplification. This possibility warrants careful experimental design and cautious interpretation of heteroplasmic results.
Studies of somatic mitochondrial DNA mutations have become an important aspect of cancer research because these mutations might have functional significance and/or serve as a biosensor for tumor detection. Here we report somatic mitochondrial DNA mutations from three specific tissue types (tumor, adjacent benign, and distant benign) recovered from 24 prostatectomy samples. Needle biopsy tissue from 12 individuals referred for prostate biopsy, yet histologically benign (symptomatic benign), were used as among individual control samples. We also sampled blood (germplasm tissue) from each patient to serve as within individual controls relative to the somatic tissues sampled (malignant, adjacent, and distant benign). Complete mitochondrial genome sequencing was attempted on each sample. In contrast to both control groups [within patient (blood) and among patient (symptomatic benign)], all of the tissue types recovered from the malignant group harbored significantly different mitochondrial DNA (mtDNA) mutations. We conclude that mitochondrial genome mutations are an early indicator of malignant transformation in prostate tissue. These mutations occur well before changes in tissue histo-pathology, indicative of prostate cancer, are evident to the pathologist.
We report the usefulness of a 3.4-kb mitochondrial genome deletion (3.4 mtdelta) for molecular definition of benign, malignant, and proximal to malignant (PTM) prostate needle biopsy specimens. The 3.4 mtdelta was identified through long-extension polymerase chain reaction (PCR) analysis of frozen prostate cancer samples. A quantitative PCR assay was developed to measure the levels of the 3.4 mtdelta in clinical samples. For normalization, amplifications of a nuclear target and total mitochondrial DNA were included. Cycle threshold data from these targets were used to calculate a score for each biopsy sample. In a pilot study of 38 benign, 29 malignant, and 41 PTM biopsy specimens, the difference between benign and malignant core biopsy specimens was well differentiated (P & .0001), with PTM indistinguishable from malignant samples (P = .833). Results of a larger study were identical. In comparison with histopathologic examination for benign and malignant samples, the sensitivity and specificity were 80% and 71%, respectively, and the area under a receiver operating characteristic (ROC) curve was 0.83 for the deletion. In a blinded external validation study, the sensitivity and specificity were 83% and 79%, and the area under the ROC curve was 0.87. The 3.4 mtdelta may be useful in defining malignant, benign, and PTM prostate tissues.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.