Aneuploidy Approaching a Perfect Score in Predicting and Preventing Cancer: Highlights from a Conference Held in Oakland, CA in January, 2004

Duesberg, Peter H.; Li, Ruhong; Rasnick, David

doi:10.4161/cc.3.6.938

Cited by 30 publications

(8 citation statements)

References 44 publications

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“…28,[136][137][138][139][140][141][142][143][144] Since this happened, although there was no consistent underlying theory, the success of these tests lends unbiased clinical proof to the speciation theory of carcinogenesis. 145,146 In sum, (a) the early presence of random aneuploidy in hyperplastic or dysplastic or transformed cells exposed to carcinogens and (b) the late appearance of cancers with individual clonal karyotypes long after primary aneuploidization, confirm the speciation cancer theory. Thus periods using nitrosourea as carcinogen.…”

Section: O N O T D I S T R I B U T Ementioning

confidence: 65%

Is carcinogenesis a form of speciation?

Duesberg

Mandrioli²,

McCormack³

et al. 2011

Cell Cycle

Self Cite

113

138

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Section: O N O T D I S T R I B U T Ementioning

confidence: 65%

Is carcinogenesis a form of speciation?

Duesberg

Mandrioli²,

McCormack³

et al. 2011

Cell Cycle

Self Cite

113

138

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“…Duesberg et al pointed out that aneuploid cancers are generally considered to be more dangerous and aggressive than the diploid [31]. Boecking et al carried out a prospective study to determine the progression to malignancy of cervical smears with ASCUS [32].…”

Section: Discussionmentioning

confidence: 99%

Correlation of DNA Ploidy with Progression of Cervical Cancer

Singh

Mehrotra

Kalra

et al. 2008

Journal of Cancer Epidemiology

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The majority of squamous cell carcinomas of cervix are preceded by visible changes in the cervix, most often detected by cervical smear. As cervical cancer is preceded by long precancerous stages, identification of the high-risk population through detection of DNA ploidy may be of importance in effective management of this disease. Here we attempted to correlate aneuploid DNA patterns and their influence on biological behavior of flow-cytometry analysis of DNA ploidy which was carried out in cytologically diagnosed cases of mild (79), moderate (36), and severe (12) dysplasia, as well as “atypical squamous cells of unknown significance (ASCUS)” (57) along with controls (69), in order to understand its importance in malignant progression of disease. Cytologically diagnosed dysplasias, which were employed for DNA ploidy studies, 39 mild, 28 moderate, and 11 severe dysplasia cases were found to be aneuploid. Out of the 69 control subjects, 6 cases showed aneuploidy pattern and the rest 63 subjects were diploid. An aneuploidy pattern was observed in 8 out of 57 cases of cytologically evaluated ASCUS. The results of the followup studies showed that aberrant DNA content reliably predicts the occurrence of squamous cell carcinoma in cervical smear. Flow cytometric analysis of DNA ploidy may provide a strategic diagnostic tool for early detection of carcinoma cervix. Therefore, it is a concept of an HPV screening with reflex cytology in combination with DNA flow cytometry to detect progressive lesions with the greatest possible sensitivity and specificity.

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“…This suggests that over time, persistent cyclin D1 expression may contribute to the "mutator phenotype" that results in the acquisition of specific genetic abnormalities during the process of carcinogenesis (1, 2, 42). In addition, the marked mitotic abnormalities seen in this study suggest that overexpression of cyclin D1 may predispose to widespread random aneuploidy that underlies the "aneuploidycancer theory," which holds that malignancy is induced by the abnormal dosage of a large number of genes (44). Notably, transgenic mice with hepatic cyclin D1 expression were noted to have aberrant hepatocyte mitotic figures prior to the development of frank malignancy, suggesting that abnormalities of the mitotic apparatus were induced early during the oncogenic process (40).…”

Section: Discussionmentioning

confidence: 99%

Short Term Cyclin D1 Overexpression Induces Centrosome Amplification, Mitotic Spindle Abnormalities, and Aneuploidy

Nelsen

Kuriyama

Hirsch

et al. 2005

Journal of Biological Chemistry

114

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In normal cells, cyclin D1 is induced by growth factors and promotes progression through the G 1 phase of the cell cycle. Cyclin D1 is also an oncogene that is thought to act primarily by bypassing the requirement for mitogens during the G 1 phase. Studies of clinical tumors have found that cyclin D1 overexpression is associated with chromosome abnormalities, although a causal effect has not been established in experimental systems. In this study, we found that transient expression of cyclin D1 in normal hepatocytes in vivo triggered dysplastic mitoses, accumulation of supernumerary centrosomes, abnormalities of the mitotic spindle, and marked chromosome changes within several days. This was associated with up-regulation of checkpoint genes p53 and p21 as well as hepatocyte apoptosis in the liver. Transient transfection of cyclin D1 also induced centrosome and mitotic spindle abnormalities in breast epithelial cells, suggesting that this may be a generalized effect. These results indicate that cyclin D1 can induce deregulation of the mitotic apparatus and aneuploidy, effects that could contribute to the role of this oncogene in malignancy.

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Aneuploidy Approaching a Perfect Score in Predicting and Preventing Cancer: Highlights from a Conference Held in Oakland, CA in January, 2004

Cited by 30 publications

References 44 publications

Is carcinogenesis a form of speciation?

Is carcinogenesis a form of speciation?

Correlation of DNA Ploidy with Progression of Cervical Cancer

Short Term Cyclin D1 Overexpression Induces Centrosome Amplification, Mitotic Spindle Abnormalities, and Aneuploidy

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