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Hello, my name is John Burn.
I'm Professor of
Clinical Genetics
at Newcastle University.
I have a special interest
in hereditary cancers
and their prevention.
I'd like to talk to you today
about mismatch repair
deficiency and Lynch syndrome.
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We named this syndrome
after Henry Lynch
who was a gastroenterologist
in Omaha, Nebraska.
He spent many years
popularizing the fact
that in some families,
colorectal and other
cancers seem to run
as a hereditary trait,
as a simple dominant trait.
This is a family that was
pivotal in the discovery
of the underlying cause
of this syndrome,
a family from the
North of England,
where as you can see
shaded in yellow,
multiple members of
the family developed
mostly colorectal but
also endometrial cancers.
We shared DNA from this
family with a team in Boston
who had an idea from
their work on yeast,
which proved to be correct,
that the underlying causative
gene was the MSH2 gene.
That was published in
1993 and subsequently
we realized this is actually
a very common condition.
We're now tracking
more than 8000 people
across Europe and beyond
with this condition
to look at the pattern
of the disease.
You can see that
by the age of 75
about 80 percent of people
with an MSH2 pathogenic variant
will develop cancer in
one of multiple areas,
particularly of the colon
endometrium and
urothelial tract.
This is one of four
genes from this system
which has been implicated
in the underlying cause
of Lynch Syndrome.
MSH2 pairs up with MSH6
and MLH1 with PMS2.
There's repair clamp
around mismatches
where the replication
of DNA has gone wrong
and it needs to be corrected,
and there is a physical failure
of the bases to combine
which is identified
by this system.
We now know that at
least one in 300 people
carry a pathogenic variant
in one of these four genes
with differing patterns
of cancer as a result.
