I'm Koorosh Korfi, I'm a senior scientist at Barts Cancer Institute in London,
and I'm also part of a UK-wide precision medicine for aggressive lymphoma consortium.
The title of this lecture,
is "Advances in Diagnostic and Therapeutic Intervention in Germinal Center Lymphomas",
and I will be using follicular lymphoma as an example.
This lecture has been co-authored by myself and Professor Jude Fitzgibbon.
What I'm going to talk to you about will
be technological advances that help us drive precision medicine,
and with that, I would delve into follicular lymphoma,
hematologic malignancy and what we know about the genetic landscape of this disease.
And following that, I'll be talking about the advances
we've made in patient stratification at diagnosis,
as well as, the Novel therapeutic strategies,
as part of this precision medicine approach.
I would be also talking briefly about the Clonal evolution and
heterogeneity paradigms as ever-evolving challenges in cancer treatment and management.
Since, follicular lymphoma is a hematologic malignancy,
I'd like to reposition ourselves to think back
about cancer as a whole and what goes wrong in cancer.
The cellular phenotype and the function of our tissues and organs is
tightly regulated by four different layers of information.
As you can see here, schematically represented, in essential for our cells and in our nuclei,
we have chromosomal structures,
which are made of our genetic code on DNA molecules, wrapped in,
what we call epigenetic marks which
consist of histone modifications and DNA methylation,
that dictate the accessibility of this genetic code
for downstream expression of our coding genes.
And you can see the next level of inflammation,
is transcription which encodes messenger RNAs and following that,
the final layer of information comes in the format
of proteins which are translated from mRNAs.
And you can imagine any aberrations in any of
these four layers of information can result in a disease such as cancer.
On the right-hand side, you can see what changes the level of
DNA can we expect information of disease, such as cancer.
So, we have 20,000 and so coding genes in our DNA.
That only accounts for two percent of our genome, but more interestingly,
the rest of our genome,
98 percent of that is a non-coding genome that is regulating these coding genes,
and also encodes for more than 20,000 non-coding RNAs.
So, you can see the complexity of
genetics in a single-cell and what can go wrong in the case of a disease.
But that's not everything,
and we know that abnormalities at the level of transcription can
also result in abnormal expression of these genes.
And also, abnormalities at the level of epigenetics such as,
DNA methylation and histone modifications can
also make differences in accessibility of
this genetic material for downstream expression of these genes.
And of course, at the final layer we can also have abnormalities of
the protein folding and post-translational modifications.
This is a simplistic view of a lot of things that can go wrong in cancer.
So really the question is,
how can we identify these abnormalities in a disease
setting such as cancer and in an individual?
And basically to answer that,
we need to know what tools do we have.
It's been fascinating over the past decade how far we've come