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  • Response to Letter to the Editor
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Response

Response to ‘Validating a gene expression signature proposed to differentiate liposarcomas that use different telomere maintenance mechanisms’

Oncogene volume 31, pages 267–268 (2012)Cite this article

In response to the above letter, our study aimed to uncover molecular mechanisms and networks of gene expression regulating telomere maintenance mechanisms (TMM) in liposarcoma (Lafferty-Whyte et al., 2009). An important aspect of our study was to derive several gene signatures associated with TMM, but we also showed network analysis and functional validation including QPCR and western blotting for some of the signature gene products in a range of cell lines. Tumours of mesenchymal origin including liposarcomas are underserved in cancer biology, and we welcome advances made through peer-reviewed publication in this field. For reasons described below, we are largely limiting this response to the data set presented to us in March 2010. Although the letter makes some interesting points, it is a very preliminary analysis and so its conclusions must remain unsubstantiated. However, a number of technical differences between our respective analyses are described below. Interestingly, despite these differences it would appear that the new data set supports the conclusions made in our publication.

We also note that some sample handling information is missing from the submission: although fresh freezing is specified in previous publications on the referenced part of the set provided by the Fox Chase Cancer Centre (Johnson et al., 2005, 2007), no information is given for the unpublished samples provided from other sources cited in the submission. This may be an important issue: it is essential to ensure that the main contributing factor to intergroup variation in microarray data is biological and not technical variance. Unfortunately, principal component analysis (PCA) performed on only telomerase and alternative lengthening of telomeres (ALT) samples from the new data set mentioned in the letter above suggests that the technical variation corresponding to the date the arrays were scanned is the largest contributing factor for sample grouping (Figure 1, below) and outweighs any biological factor, including histological subtype and TMM. This will therefore confound any clustering results.

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Figure 1

References

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Authors and Affiliations

  1. Institute of Cancer Sciences, University of Glasgow, Cancer Research UK Beatson Laboratories, Glasgow, UK

    W N Keith, K Lafferty-Whyte, C J Cairney & A Bilsland

  2. Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

    N Zaffaroni

Authors
  1. W N Keith
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  2. K Lafferty-Whyte
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  3. C J Cairney
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  4. N Zaffaroni
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  5. A Bilsland
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Correspondence to W N Keith.

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Keith, W., Lafferty-Whyte, K., Cairney, C. et al. Response to ‘Validating a gene expression signature proposed to differentiate liposarcomas that use different telomere maintenance mechanisms’. Oncogene 31, 267–268 (2012). https://doi.org/10.1038/onc.2011.374

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