Jean Claude Zenklusen: I was going to go with the surelinger Isenberg
joke [spelled phonetically], but well, we’ll have to keep it for next time.
So, my name is Jean Claude Zenklusen.
I am the director of the TCGA Program Office at NCI.
Me and Carolyn, we get to have the pleasure, once a year, to tell you what we -- what you
all have been doing, and what we have been achieving.
And so, let’s see, we have the timeline of TCGA is something that you all are probably
familiar, but then, maybe some new faces in the room.
We started as a pilot project in 2005, 2006 with GBM and ovarian carcinoma, 500 cases
each.
It was funny -- last week, somebody asked me, “What was the power calculation that
you did in order to get to 500?”
And the answer was, “None whatsoever.
We didn’t know what was the rate of discovery.
We didn’t know what was the rate of mutations.
We didn’t know anything about this so, we just said, "How many do we have money for
and how many do we think we can get?"
And our magic number was 500.
Obviously, since then, now we have actual power calculations.
You all know the Lawrence paper, and it will be more on that later on.
In 2010, we expanded to 25 regular tumors, number of tumors plus 10 tumor types [spelled
phonetically].
We ended up doing nine of those tumor types.
We got better at doing things.
We got the pipeline down to a T, and we could generate data that with, you know, some budges
here and there, but they’re mostly, you know, non-budged and we can do the analysis
in a clean fashion.
While the face that we are at right now is the completion of the analysis.
TCGA will end effectively sometime in the spring 2016.
This is the last symposium that we have here, at natural [spelled phonetically].
Next symposium is going to be a longer and larger affair.
We are planning on a big bang to go with some fireworks.
It’s going to be a three, four-day event which we will present all the findings, one,
AWG, one analysis working group at a time, and then the PanCan analysis, and then we
are going to have a lot of people invited that are using the data that are not part
of the team.
So, it’s going to be a big thing.
Stay tuned for that one.
We are negotiating with some association which will remain nameless until they say yes.
We’re trying to make it a big joint meeting.
It’s going to happen in D.C.
It’s still, you know, the federal government, they don’t like us to travel that much.
So, it’s still going to be here.
So you are all going to be welcome to D.C. once again.
We’ll announce it when we have more details, obviously.
This is the tumor project progress.
As you can see, the red bars are manuscripts submitted or published.
We are past the mid-point here.
All of the tumor types that were selected for analysis except for the diffuse large
B-cell lymphomas were actually analyzed.
We have the data and we have, as you see, all that sea of green there, is all the analysis
working groups that are active at the moment.
And this is for primary analysis.
We have some other Analysis Working Groups that are for secondary papers.
Things like the combination between LGG and GBMs, recurrence LGGs, lower the risk of cancer,
which is submitting a manuscript very, very soon.
So, we have other things that are not represented here, but as you can see, we are nearing the
end of our task.
This is the data we have available.
We don’t expect too much more data to come in.
There are some samples that had needed some sequencing top off [spelled phonetically]
that will appear soon, but basically we have gotten 12,550 cases that were qualified.
Our goal was 10,000 so, we did well there.
A bunch of them were received at the end of December.
In fact, one-eighth of them, probably because we’re closing the doors on people who tried
to, you know, put a foot inside.
We have, at the moment, 10,849 with minimal clinical data sets, meaning the enrollment
data, and we have 8,404 with at least one year follow-up.
And as you can see, the higher year numbers are filling up.
Last time I gave this talk, we had two cases with four years.
Now, we have 19.
People keep giving the clinical data, and we will accept it.
We will move all these data, both TCGA, target, CGCI to a new system called the NCI Genomics
Data Commons, GDC for short.
And the GDC will keep accepting clinical data if you have it and you want to submit it.
Obviously, the contracts are done for the tissue source size [spelled phonetically]
that are sitting in the audience, the contracts are done.
So, all the data that you provide will be for the good of humanity.
No checks will be cut on that data.
We are done with the payments.
155,000-plus samples of RNA and DNA protein were shipped to date.
And all but 9,429 samples have data returned, which means that we have 99.8 percent of all
samples with data and 94 percent of the cases have at least some Level one data publicly
available.
The samples, these aliquots that don’t have data are probably never going to have data.
These are aliquots that were destroyed, they were no good, they dried out, you know, things
happen in transit.
And so this is basically a fairly good track record if you look at it.
Almost 100 percent of cases, just .2 percent of cases, did not get to be processed, which,
looking at the size of this project, is short of a miracle.
So, I think, you know, the data generators did very well.
The VCR did splendid.
No complaints here.
So, what Analysis Working Groups we have going, you can read the list.
I’m not going to read it for you.
Some of them are, as I said, for example, LGG, GBM, they are secondary efforts.
We are going to have more of those secondary efforts.
Obviously, the level of support that we can give to a secondary effort is a lot less than
we give to the primary papers.
The reason is we have 13 primaries that are still active.
This is really the most active time in the analysis.
And so we don’t have much bandwidth left for anybody, but we’ll support you as much
as we can.
These are our recent publications, recent being a year, year and a half.
Some were recently accepted.
Skin and low grade glioma accepted to sell in New England Journal of Medicine.
And then a cortical [spelled phonetically] is in the process of being reviewed in Nature
Genetics, and there are at least four others that are very close to be submitted.
So, our production -- our manuscript production has come into year two as the analysis has
continued.
And in fact, one of the things that we’re seeing is that the rare tumor types, because
they have all the data upfront before the AGG starts working, they’re moving extremely
fast.
That also happens because we have some very eager co-chairs that are pushing for this
to be done on time and fast.
But, you know, the fact to have all the data ahead of time helps a lot.
It also helps that the number of tumors is smaller so, the data gets analyzed faster.
Oh, I’m sorry.
There will be no TCGA 2.0.
Those four letters are great for sequencing.
They’re not too good for programs anymore, okay?
Programs should have a sunset.
When we have sunsets in programs, we have goals that can be achieved.
We don’t want to produce a program that is an entitlement, okay?
So, TCGA reached its goal, did all the things we set out to do and more.
We can all pat ourselves on the back.
We will be done next year, and that’s the end.
That’s not the end of cancer genomics, of course not.
NCI is committed to it, and we have several different projects that are already launched,
or are about to be launched.
Some of them have more of a discovery phase to it, like CDDP, the Cancer Driver Discovery
Project.
Some of them have more of a clinical bias to them, like, ALCHEMIST, which is a lung
trial that we are basically characterizing about 7,000 cases that are coming through
it.
Exceptional Responders is something similar.
It’s, as it says, those people that responded exceptionally to drugs that were not -- they
were not approved by FDA, and the trial was not successful.
But still, we want to see why these people actually had a good response and we do it
through sequencing.
And the CTSP, which is the Clinical Trial and Sequencing Program, which is open right
now for applications, and it’s a program that is a joint program between the Center
for Cancer Genomics and the Division for Cancer Treatment and Diagnostic.
Basically, we’ll take probably two clinical trials that are well done.
I have enough samples and the samples are of good shape and we’ll sequence them up
to figure out, you know, what their results were.
The bias that we’re going to have for all future cancer genomic programs is a bias towards
explaining what happens at the clinic.
TCGA was great as discovery, we were not so good at clinical.
We were not meant to be so good at clinical.
These projects are going to be focused on clinical samples that still have good outcomes.
So, we can ask clinical questions that we were not able to ask in TCGA.
So, if you want more about that, you can see me at the breaks and then we can discuss them.
CDDP is focused on lung, colon, and ovarian.
We have identified lung and colon cohorts.
We can always use more ovarian cohorts, so if you have them, you have a -- even a small
trial, you know, 100, 150 cases, we’ll take them if they have all the requirements.
Don’t come and tell me, “I have two patients,” because, you know, that’s not good enough.
We need to have numbers and we need to have numbers that were collected consistently.
The message, basically, is that cancer genomics is here to stay, but in the context of helping
figure out how to get -- to treat the patient, not just in the context of, “Well, I have
this other mutation [spelled phonetically].”
On the role of doing that, we are going to get to the, “Ooh, I have this other mutation
that I had not identified before,” because we’re going to have more cases, but that’s
not the focus of this programs.
Okay, and with that, I invite Carolyn to come up, and if you can get her first light [spelled
phonetically], I’ll stay around because --
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