Molecular genetics of non-Hodgkin lymphoma

Published on November 30, 2015   33 min

Other Talks in the Series: Cancer Genetics

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My name is Jude Fitzgibbon. I am a Professor in Personalized Cancer Medicine at the Barts Cancer Institute. It's part of Queen Mary University of London. My lecture today is on the Molecular Genetics of Non-Hodgkin Lymphoma. I am going to be using an indolent B-cell malignancy called follicular lymphoma as an example.
I think it's important to preset that cancer represents almost the perfect genetic disease where it's radicalized maybe 10-20 genes to actually shift the balance from a normalcy to a malignant phenotype. And so we need to think of these genes as individuals but also how they kind of work together to cooperate to actually drive this change in phenotype. And it's helpful to think of a formula in relationship to cancer and indeed B-cell malignancy in relationship to the genetics and the microenvironment working together to give rise to cancer.
The technology has improved fantastically. When I started my PhD in the late '80s, you know, I did my first polymerase chain reaction, my first PCRs using three water baths set at different temperatures, a stopwatch, and a tweezers to actually move the chews from one place to another. Now we've got the opportunity to actually sample all genes, all DNA in one single experiment and monitor their expression at the same time.
So I think what we should do is we should try and get a very clear picture of what the human genome is. So if we can imagine the human genome as a stadium of 25,000 spectators, that corresponds to 25,000 genes. We know where each spectator, where each gene lies. We know the location and the position, and then we know exactly what they look like because that's their DNA sequence. And how they sound because that's the sequence of their messenger RNA. We've now the tools to define the DNA and the mRNA profiles of every cancerous cell in single experiments where we can focus in on the whole genome, that's the three billion base pairs of sequence. If we're just interested in looking at the coding sequence, which is less than 2 percent of the genome, we can focus in on 50 mega bases. But what's ideal is when we know the key genes that we know to be important, we can focus in on those using other different technologies. Now what's also key is to preset that we're not just looking at genes here because these are not just genes, they're genes with clothes on. So you can see the spectators have specific clothes on. And it's that combination of the gene sequence itself, but also the control of gene expression and gene function via epigenetics. That's key in this shift from normalcy to the tumor phenotype.