"While the story is basically one long anecdote that shows what can be done when new genomic technologies are applied to cancer, it also shows why we are a very long way from the true 'individualization' of cancer care.
. . . .
"Taking the results of the sequencing of the entire genome and RNAseq data and analyzing them allows scientists to probe the genome and transcriptome of cancers in a way that was never before possible. It produces an enormous amount of data, too, terabytes from a single experiment. At cancer meetings I’ve been to, investigators frequently refer to a 'firehose' of data, petabytes in magnitude. Indeed, the sheer quantity of data from these experiments challenges the bandwidth of universities doing them, and, in fact, it’s not at all uncommon for the preferred means of sending experimental data to be to load up a hard drive with the data and send it by the quaint but effective method of overnight mail to other investigators because it’s faster and more reliable that way. Not surprisingly, serious computing power and major advancements in computer algorithms have been necessary to develop the methods of analyzing data from these experiments.
"What I’m trying to convey is that what WUSTL did for Dr. Wartman was not a little deal. It was a big deal that took a lot of resources and effort and likely cost well over $100,000. Apparently it was paid for through research grants, and Dr. Ley claims that no patients were neglected while all that sequencing and computing firepower were transferred to sequencing Dr. Wartman’s cancer genome and transcriptome, having done the same thing for a previous patient."
In other words, the glimpse of the future that we may be able to derive from this case shows that the future is still far off, and the steps to reach the future are enormously expensive. More details are available in other paragraphs of the linked Science-Based Medicine post.
But the lab succeeded, and now we have an example that DNA/RNA sequencing may be useful for the treatment of cancer. Not only that but it sounds like we learned something about a particular strain of Leukemia afflicting at least one person, but probably several more. I am sure the Drug company/ies are relived to discover that their drug might be useful for treating other types of cancer.
And I think a truck full of hard drives hurdling down the highway has had greater bandwidth than most of the world's networking for a while now.
As the future of medicine is clearly personalized I think the costs associates with genome sequencing and other analysis will come down. Or, at least, I hope they do.
In other words, this was a $100,000 diagnostic test with no guarantee that an actionable diagnosis would result. By that, I mean that the results of the sequencing analysis either (a) might not pinpoint a driver mutation or (b) might pinpoint a driver mutation that does not have an efficacious drug available to act on that mutation. Also, all caveats about tumor heterogeneity and evolution, etc., apply.
An integrating sequencing approach involving the analysis of normal and cancerous cells to identify actionable mutations is the best we have for now, but it is still a hugely expensive, time-consuming, and technically-challenging process with an enormous failure rate associated with it. Nonetheless, I think it's terrific that, in this instance, it yielded valuable and actionable information that resulted in a meaningful clinical result. One step at a time!
And the problems he is listing, all it takes is something like memristors to catch on to lay waste to his worries on data and computational limits and replace them with "I remember back in the day when petabytes were considered a firehose".
And looking at the price to sequence DNA -- I have seen little, if anything, that ever crashed that fast.
Even worse is the fact that our ability to sequence is increasing faster than our ability to process the data.
The cancer that he had was clearly his own, as evidenced by the fact that they were able to match up his normal genome with the tumor genome and find the handful of differences that were driving the cancer.
*Full disclosure: I work in the Genome Institute at WashU, where this sequencing was done, and while I did not work on this particular case, this sort of cancer genomics project is what I work on all day long.
The reason tasmanian devils can transmit cancer is that they're not genetically diverse enough to differentiate foreign cells from their own cells. But that's the exception that proves the rule: tasmanian devils are unusual in that they went through recent population bottlenecks that dramatically reduced their genetic diversity.
Part 2 : A New Treatment’s Tantalizing Promise Brings Heartbreaking Ups and Downs
Part3 : A new genetic test of ocular melanomas offers uncanny accuracy, but do you want to know ?
( HN : http://news.ycombinator.com/item?id=4220123 )
The other product that 23andMe is starting to offer is exome sequencing, where they analyze just the coding regions of the genome (around 1% of the total content). This sort of analysis can be enormously useful and can provide much information, but will miss variations in non-coding regions. It also has limited ability to detect structural variations, where a chunk of DNA gets moved around, deleted, or duplicated.
What they did here was whole genome analysis, coupled with sequencing the RNA products of gene expression. This turned out to be enormously important, because the main driver of his cancer turned out to be over-expression of a gene.
This is indeed the case for most mutations that we're finding in cancer genomes. (That's the bad news).
The good news is that many cancers do have "druggable" genes that are altered, and even though the cells have many mutations, attacking just the druggable gene is often enough to prolong life and improve outcomes.
The other good news is that even though many different genes can be mutated, there are a much smaller number of pathways that are altered. (those for cell cycle control, apoptosis, etc). By targeting key points in those pathways, one drug may be effective against dozens of different mutations.