The DNA-instability test as a specific marker of malignancy and its application to detect cancer clones in borderline malignancy

Abstract

Recent progress in cytogenetic and biochemical mutator assay technologies has enabled us to detect single gene alterations and gross chromosomal rearrangements, and it became clear that all cancer cells are genetically unstable. In order to detect the genome-wide instability of cancer cells, a new simple method, the DNA-instability test, was developed. The methods to detect genomic instability so far reported have only demonstrated the presence of qualitative and quantitative alterations in certain specific genomic loci. In contrast to these commonly used methods to reveal the genomic instability at certain specific DNA regions, the newly introduced DNA-instability test revealed the presence of physical DNA-instability in the entire DNA molecule of a cancer cell nucleus as revealed by increased liability to denature upon HCl hydrolysis or formamide exposure. When this test was applied to borderline malignancies, cancer clones were detected in all cases at an early-stage of cancer progression. We proposed a new concept of "procancer" clones to define those cancer clones with "functional atypia" showing positivities for various cancer markers, as well as DNA-instability testing, but showing no remarkable ordinary "morphological atypia" which is commonly used as the basis of histopathological diagnosis of malignancy.

PAMAM Structure‐Based Multifunctional Fluorescent Conjugates for Improved Fluorescent Labelling of Biomacromolecules

“…[8] In oncology, in vitro fluorescence labelling techniques have become increasingly interesting because they allow the determination of tumour malignancy, [9] chromosomal abnormalities, [10] metastatic disposition of tumours, [11] tumour oxygenation and pH, [12] tumour-induced angiogenesis, [13] gene deletions, duplications and amplifications [14] and also apoptosis versus necrosis imaging in cancer cell lines. [15] An emerging application of fluorescent compounds is diagnostic imaging in vivo, which allows an estimation of the metastatic disposition of tumours, [16] the detection of tumour-associated enzymes [17] and single cells in living orAbstract: Fluorescent probes are of increasing interest in medicinal and biological applications for the elucidation of the structures and functions of healthy as well as tumour cells.…”

Comparative study of Western and Japanese criteria for biopsy-based diagnosis of gastric epithelial neoplasia

“…From a Western point of view, the final diagnosis rests on examination of the surgical or ESD specimen, because there is some possibility of cancer even if the diagnosis is LGD or HGD [21,23,36,[46][47][48]. Some studies have indicated that LGD and HGD should be treated, because genomic instability may already be present [49][50][51][52]. However, the European guidelines recommend reassessment with biopsy sampling and surveillance at 6-month to 1-year intervals for patients with HGD in the absence of endoscopically defined lesions [8].…”

Nuclear histochemistry: Its history in fifty volumes

“…This attitude has become especially apparent during the last few years, when several papers have been published which deserve high interest from the viewpoint of both the improvement of methodology (Mazzini et al, 2003;Bottiroli et al, 2004;Cremer et al, 2004;Pederson, 2004;Marziliano ey al. 2005;Sheval et al, 2005) and the application to clinical research (Alexandrakis et al, 2005;Fukuda et al, 2005;Hirose et al, 2005;Soldani et al, 2005).…”