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Drilling down to the Single Cell Level

Date: 27 Jul 2010
Member: Neil Winegarden


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Thoughts and news on single cell analysis
Welcome (if anyone actually reads this - otherwise I'm talking to myself).

I've often thought one of the big disappointments for genomic science has been that despite 15 years or so of research, we've really not made much impact on diseases such as cancer. Don't get me wrong, we have a much better understanding of this complex set of diseases, but in reality there are very few of the prognostic and diagnostic tests that were promised when technologies such as microarrays lept onto the scene. Look at a disease such as lung cancer. My colleagues here at the University Health Network have shocked me with some of their findings in terms of prognostic gene signatures for non-small cell lung cancer. Looking at several different published prognostic profiles they found that only one gene overlapped them all (and that gene itself is not sufficient for any sort of stratification). Furthermore they found that over 1000 different 6-gene signatures could be identified in a single microarray dataset that had prognostic value.

So the question is - why is this the case? In my view of things, I think a lot of this is due to the heterogeneity of diseases such as lung cancer. To date, the vast majority of genomic analyses on cancers have involved bulk tumour profiling. Differences in cellular make up, percentage of tumour etc play huge parts in determining the signatures obtained. The fact that different surgeons and pathologists will have different techniques for the excision of the tissue may even explain why there are variations among institutions.

Now that LCM is becoming a common practise we are starting to see that data sets are more comparable. Analysis of just the epithelial or stromal compartment of a tumour means a more homogeneous population is examined. But to do this we need extreme sensitivity in our 'omics approaches. Being able to drill down to the single cell will mean we can really tackle the issue of "tumour stem cells" as well. Purification methodologies that only provide a 1:100 level of purity are still insufficient as the signature of the most important cell only contributes to 1% of the total profile. It will be new, affordable and robust single cell technologies that will finally help us realise the promise of genomics I believe.

Last Updated on 27 Jul 2010

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