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Tumor Biology

, Volume 35, Issue 11, pp 11311–11318

First Online: 14 August 2014Received: 26 March 2014Accepted: 04 August 2014

Abstract

One of the most crucial concerns of cancer research pertains to the differences between the neoplastic cells in tumor specimens in vivo and their counterparts in cell lines. The huge amount of results deposited in cancer genetic databases allows to address this issue from a wider perspective. Our analysis of the Sanger Institute Catalog Of Somatic Mutations In Cancer COSMIC database v61 showed a lower percentage of homozygous mutations in a group of tumor suppressor genes in surgical samples in vivo in comparison to their frequency in cell lines in vitro. Similarly, the mutations resulting in the lack of protein e.g., nonsense mutations or whole gene deletions of several tumor suppressor genes TSGs were more frequently observed in vitro than in vivo. In this article, we suggest two potential explanations of these data. Firstly, TSG heterozygous mutations resulting in the modified protein e.g., missense mutations may be gradually when the specific molecular context is achieved changed to homozygous mutations resulting in the lack of protein during carcinogenesis. Secondly, among different independent pathways of tumorigenesis, those leading to homozygous nonsense mutations are characteristic for cells which are more efficiently stabilized in vitro. To conclude, these observations may be interesting for researchers working with cell line in vitro models illustrating the extent to which they reflect the tumors in vivo.

KeywordsTumor suppressor genes Quasi-sufficiency Three hits hypothesis Two hits hypothesis Ewelina Stoczynska-Fidelus and Michal Bienkowski equally contributed.

Electronic supplementary materialThe online version of this article doi:10.1007-s13277-014-2444-5 contains supplementary material, which is available to authorized users.

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Author: Ewelina Stoczynska-Fidelus - Michal Bienkowski - Marcin Pacholczyk - Marta Winiecka-Klimek - Mateusz Banaszczyk - Jolanta Zi

Source: https://link.springer.com/article/10.1007/s13277-014-2444-5



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