Kenna Shaw: So I might try to stall a little bit.
Our second speaker has not quite gotten through traffic yet.
[laughs] That said, I think I'm going to go ahead and start.
I think everybody in this audience obviously knows why TCGA exists and what our core objectives
are, but I did want to review for some of the folks that might not know all of the history
that when TCGA was launched in 2006, we did start as a pilot, and the pilot was to go
after GBM, lung squamous, and ovarian cystadenocarcinoma.
And in 2009, we expanded, I think, now as many of you know, obviously, to 20 new tumor
types, and I'm going to announce again kind of a somewhat broader expansion even to some
new rare tumor types that we hope to finish by the end of next year.
In order to stay on our current timeline we would like to complete all acquisition to
get to 11,000 qualified cases, which would account for the pilot phase of about 1,000
cases, which was our goal, and to the 10,000 case expansion.
And as of today, we have about, almost, 8,000 qualified cases sitting at the BCR or having
been shipped, so we're very close to that goal, and by the end of this year we should
hit that 8,000 out of 11,000 mark.
The goals of TCGA remain the same today as they were in 2006, and that's to establish
and demonstrate that team science can be an effective way to getting large datasets out
to the community, that federal government and very, very talented scientists can develop
a scalable pipeline that we've always stressed begins with the highest quality samples.
And about 20 percent of the audience today are the folks that are providing those clinical
samples that make this project possible.
And we have representatives also here, just to kind of hint, from SAIC-Frederick who are
helping us continue the sample acquisition phase now, that if you have samples, we still
want them, so that's always going to be my bottom line.
We've determined, I think, that we can develop a large scale parts list and make it publicly
accessible, and we want to do this always on statistically robust sample sets, which
is why TCGA tends to go after 500 qualified cases of every diagnosis we look at, at least
for our major tumor types.
Again, the rare tumors are going to be an exception to that rule, and we always make
the data publicly available.
In fact, most of our investigators actually upload the data to the public domain and then
download it before they actually do their own analysis.
So TCGA has stayed true to a "no platform left behind" strategy, which I know frustrates
some, but I think still provides the most comprehensive dataset to the community, and
therefore, I think, is really living up to its -- what we tried to do initially.
And so for every tumor type -- every sample that comes in we have an array of data that
come out, and this is done right now through just over 150 tissue source sites all around
the globe.
We have tissue source sites in Pakistan, in Moscow, in Thailand, in Vietnam, in -- a new
one in Colombia, South America and even all the way to Hawaii.
So they're all over the world.
We do this with six cancer genomic characterization centers in the sequencing centers from NHGRI,
and we've also added these seven genome data analysis centers that try to provide integrated
analysis and portals for the community to utilize.
And, of course, we have the data coordinating centers with SRA International that provides
all non-primary sequence data, and CG Hub now at UCSC that provides the sequencing data
the community.
While this is small, I wanted to make sure that at least people had it available online.
This is the current TCGA research network.
There are some changes.
We've recently consolidated all samples to be sent to our Columbus, Ohio Biospecimen
Core Resource, so Julie Gastier-Foster is here if you have questions about how the BCR
works.
All samples are now flowing through a single unified pipeline at Nationwide Children's.
We've added UCSC as a data portal for our sequence data away from NCBI, and I'll go
over that briefly at the end.
So here, if you have a favorite tumor, you're going to want to look along the bottom of
our x-axis, and along the y, you'll see how many qualified cases have either been shipped
or have qualified and are ready to be shipped from the BCR.
If it has an asterisk on top it means we've basically closed acquisition and are only
open to specific acquisition from African-American patients or patients who would be racially
defined as black on a census form, essentially, so anywhere in the world we would take your
samples as long as they qualified under that racial category.
If you are in a -- if your favorite tumor type is under a green bar, we are actively
doing analysis and or preparing a manuscript right now.
If you're in blue or even if you're in green and are on this end of the spectrum, this
is where I'm bugging -- you probably know me well because I've bugged you on email,
or on the phone, or in person at your house to try to get samples out of your freezers.
I've yet to do that, but I'm getting very, very close, so don't leave your addresses
with Josh outside.
You'll see this, my favorite new little bar here, is this gold bar for chromophobe kidney.
This is our first rare tumor type that we ventured into with TCGA, and I'm going to
introduce this project to many in the audience today for the first time.
So it became very clear, if you looked at our sample acquisition graph, with red being
where samples were coming in, and this is total unqualified cases, so this is total
cases coming in our door.
And red is the ideal curve, so to speak, to get to a number that would get to 11,000 cases
by the end of this project, and the end of this project is late summer 2014.
So in order for us to get to 11,000 qualified cases by the end of summer 2014, I have to
have 11,000 qualifiable cases into Julie and her team at the Nationwide Children's BCR
by December 15, 2013, so we've just over a year to collect about 5,000 more samples in
order to hit this metric.
It's going to be a very, very busy year I hope for us.
But the reality was that when I looked at our blue line, which is the sample, the reality
of sample acquisition with it flattening out, assuming we never collect another case, it
was clear that there was no way, with the way sample acquisition was going, that we
were going to hit, ever hit or meet this red line.
And so in order to try to fill some of at least the case acquisition gap and realizing
that many tumor types were still orphan in the international cancer genomics community
and not being tackled, we started a rare cancer project.
The first one we went after was chromophobe kidney; that is now closed to accrual.
But chromophobe kidney represents our first case where we have 50 qualified cases of a
rare tumor.
These other tumor types are currently being investigated with adrenocortical carcinoma
and uterine carcinosarcoma acquisition hopefully ending by the end of this year.
Pheochromocytoma and paraganglioma hopefully being accrued in February and March of next
year, and the other tumor types hopefully being defined as we go on.
That said, if it hasn't been done, and you have potential of 100 cases that can come
in, we will add your rare tumor as long as it's a malignant tumor type.
So come find me if you have a good idea.
And I will say thymoma is one of these examples of the last TCGA meeting we announced this,
and it was a smaller meeting, but one of our ESC members came up and was very interested
in thymoma and that's now on the potential list.
So if you have an interest in a potential we might be able to slot you in.
So between the pilot and the expansion, and now I can speed up since our second speaker
has arrived, I wanted to kind of go over what our core datasets are so that you know what
to expect, because things have absolutely changed between what we did in the pilot and
what we're doing today.
Every case now gets Affymetrix SNP 6.0 arrays, the Infinium array, which is now the 450K
array for methylation.
Every case is -- we use RNAseq for both miRNA and mRNA.
Every case gets a whole exome and 10, 10-plus percent of cases get whole genomes.
If there's enough residual tissue, we will do a Reverse Phase Protein Array with Gordon
Mills at MD Anderson.
Every case has minimum enrollment data, a pathology report, and an H&E from both the
frozen and a diagnostic slide.
So we do have several groups now that are doing genotype/phenotype correlations by trying
to add some histopathology review on top of these images and pathology reports, and those
data are slowly becoming public also.
So as of today we have 7,136 cases that have been shipped and have initial by a specimen
data at the DCC.
Those other 900 cases-ish that we have in the pipeline are basically projected because
we have them in hand, but they have not yet qualified or been shipped yet.
Five thousand eight hundred plus of those cases have a minimum clinical dataset, so
this is basic clinical data diagnosis, date of diagnosis, age of diagnosis, et cetera.
Thirty-eight hundred, 3,900 have at least one year of follow-up, and about half of those
have treatment information associated.
We are going after -- everyone asks every meeting I go to -- we are going after at least
minimum of one year follow-up, additional follow-up on all patients.
And we will go after additional years as funding allows.
So far, of those 7,100 cases, 105 samples have been shipped to our centers, so from
one single case we isolate RNA and DNA from tumor and normal, and 105 samples have been
shipped to our centers.
Eighty-seven percent of those -- 87 percent of those samples have a level one dataset
publicly available, and we are currently hunting down, with the help of Batelle and our quality
management system, we are actively hunting down what has happened to those other 13,000
one by one, and the centers have just started getting emails from me asking for those data.
And some of them we will never find because there's bad data or a bad sample, but we will
at least try to account for where every single piece of data is, but we do have an 87 percent
return rate, which means -- which is still fairly comprehensive.
So I wanted to go over the timeline briefly in hopes that the community sitting in this
room will help us shorten this timeline to getting the data out to the community.
First and foremost, this starts with sample procurement.
Without samples, we can't have a project.
And from first touch to first touch, meaning from first touch -- from the first time I
talk to a tissue source site to the first time I see a sample can be anywhere from three
months to two years.
Some of you have been working me with me for two years and have yet to ship a sample are
in this room, so you know how painful it can be to just get emails and emails and emails
from me.
It takes about 90 days at the BCR before we are able to ship -- to qualify our case and
ship it out to our centers.
SNP data, on average, rolls around about 45 days after the SIC [spelled phonetically]
cases have been shipped.
Methylation a little later, followed by miRNAseq, mRNAseq and exomes, which average about 180
days ,depending on the center doing the sequencing.
And then it takes us about 12 to 24 months from the time we have about half of the -- half
of our dataset available to get a publication into the public domain.
So from first touch to first public review, you're looking at approximately five years.
These are the people in the audience that hopefully you'll go talk to if you have questions
about any of our pipeline.
I'm mostly responsible for tissue acquisition and the characterization centers.
Roy Tarnuzzer, Martin Ferguson ,and John Demchok are responsible for help managing the BCR
with Julie Gastier, as well as clinical data, et cetera.
Brad Ozenberger from the NHGRI for the sequencing centers.
Liming runs our DCC and CGHub from the program office with a team of folks.
And I did want to recognize this very special human being right here, Julia, who really
did manage this meeting with the help of Josh Shapiro, obviously, outside.
And Margi Sheth, who most of you know from running all of -- all 20-plus of our analysis
working groups.
I'm not going to go over this slide because we're running out of time, but, again, it's
also actually in your book, our sample criteria, so I suggest if you're interested in what
our sample criteria are, you flip to the program information pages, and I have all of our really
desperately seeking tumor types list there, as well as our sample criteria.
And ultimately, of course, our end goal is to make sure that all of these high-quality
samples end up in the public domain, so that one single dataset, in this case the GBM datasets,
can lead to an immense amount of research.
So this is every single paper that's actually used the primary GBM dataset in a public -- in
a publication post-release, post-data release.
Hopefully all of you know about the TCGA data portal and getting data, the DCC from SRA
International.
The team is here today and they'll be giving a workshop this afternoon.
If you want to learn about their DCC 2.0, the revamp that should go live next year,
we hope that you'll talk to them and give them some guidance on perhaps what you're
looking for in terms of case studies for what our current DCC doesn't provide you, but you
might want to get out of a next version.
We also have the team from Firehose here, this is team from the Broad led by Gaddy Getz,
and Leonard Chin now at MD Anderson, where we have ongoing pipeline analysis, so these
are runs through their analytical engine that provide you -- so if you click on our breast
link, for example ,you'd get some information on where we are with breast cancer, and you
could even get all the way down to GISTIC plots, et cetera.
So these are almost figure level with legends et cetera, so you can get a snapshot of any
tumor type you want for the active data.
We also have, of course, representatives from David Hauser's [spelled phonetically] team
here, and NI Systems who manage the CGHub, which is our sequencing repository, which
I think most people in the room have finally gotten on to, but we have moved all of our
data to the system, and they will also be running a workshop at this meeting, so we
hope that you guys will attend if you have any questions.
I wanted to make sure also that everyone was aware that if you don't see your favorite
tumor type on the TCGA list there is a chance that the International Cancer Genomics Center
is working on your favorite tumor type, so please go to their website.
Brett Whitty, actually, is here from the ICGC data-coordinating center, so if you have questions
you can always hunt him down.
I'm sure he'll be pleased that I just did that.
I did not warn him, but he will be here to answer questions about their project as well.
I wanted to, of course, acknowledge very briefly, before turning this over to Stephen and Lou,
the team in our office, and I apologize to Greg, but you didn't send me a picture, man.
[laughs] It's all I had.
So, here is the team from the office.
Obviously, thanks also to my team of supervisors, and the direct -- co-directors for the Center
for Cancer Genomics, Stephen Chanock and Lou Staudt, as well as the team who co-manages
TCGA from NHGRI, Brad Ozenberger, Heidi Sofia, Lindsay Lund, and Mark Guyer.
And I think we'll just come up at the end if there are any questions for all of us at
the end.
[applause]