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- W1520347600 abstract "We have exploited random integrations of foreign DNA as a means of genetically tagging tumour cell populations with which to analyse the clonal evolution of tumour growth in vivo. Transfection of a non-metastatic mouse mammary carcinoma called SP1 (or a metastatic variant, SP1HU9L) with the pSV2neo plasmid or retrovirus vector infection with a ‘clipped-wing’ vector (ΔpΔeMoTN) was used to generate large numbers of uniquely marked tumour cell clones in single-step selections. The basic approach was to pool large numbers of independently marked transfectants or infectants, inject these cells into mice and analyse the resulting primary tumours and/or metastases later. Overgrowth or derivation of tumour masses by a limited number of clones could be detected by Southern gel analysis. The main findings were: (i) injection of pooled populations containing large numbers of uniquely marked cell clones (up to several thousand) invariably resulted in advanced primary tumours that contained a very limited number of clones, and in some cases only one easily detectable clone; (ii) primary tumours could be overgrown within six weeks by the progeny of the same single metastatic clone when the inoculum contained 1–10% metastatic cells, which suggests that metastatic SP1 cells have a selective growth advantage in primary tumours as well as for metastatic spread; and (iii) spontaneous lung metastases were clonal or biclonal at the time of analysis. The results show that spontaneous metastases can develop from a genetically distinct subpopulation of cells in a non-random (i.e. selective) manner. Because primary tumours can become overgrown by the progeny of a metastatic clone, results of any comparison of the properties of a primary tumour with a distant metastasis could be affected by the stage at which the primary tumour is removed and analysed." @default.
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- W1520347600 date "2007-09-28" @default.
- W1520347600 modified "2023-09-23" @default.
- W1520347600 title "Clonal Changes in Tumours During Growth and Progression Evaluated by Southern Gel Analysis of Random Integrations of Foreign DNA" @default.
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- W1520347600 doi "https://doi.org/10.1002/9780470513736.ch8" @default.
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