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I am Felix Mitelman
at the University of
Lund, in Sweden.
And my lecture
will be on the role played
by chromosome translocations
in cancer development.
I will also briefly discuss
the clinical significance
of translocations
as diagnostic
and prognostic tools
in the management
of cancer patients.
And finally, I will present
some remaining questions
as to how, when and why
the aberrations are formed.
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But first,
a historical background
as an introduction.
And an appropriate
starting point
is 100 years ago in 1914,
when Theodor Boveri
in this famous book, in English,
on the origin of cancer
presented a conceptually
new idea, which later became known
as the somatic mutation
theory of cancer.
0:57
Boveri proposed
that cancer originates
in a single cell
by mitotic disturbances
resulting
in chromosome aberrations.
Through
subsequent cell divisions,
this acquired genetic change
is propagated
to all daughter cells.
And as a consequence,
all cells in a cancer
carry the genetic abnormality
that initiated this process.
This remarkably prescient idea
still today remains
the paradigmatic view
of cancer pathogenesis
supported by
a wealth
of experimental evidence.
But it long remained
a theoretical idea,
which could not be
examined critically
until technical improvements
in human cytogenetics
were made half a century later,
and led to the description in 1956
1:51
of the normal human
chromosome complements
by Tjio and Levan
in Lund, Sweden.
1:60
Only four years later in 1960,
Peter Nowell
and David Hungerford,
in Philadelphia,
presented the first evidence
supporting Boveri's idea.
They showed that patients
with chronic myeloid leukemia
consistently had a small
acquired marked chromosome
in their bone marrow cells.
One of the smallest chromosomes,
number 21 or 22,
this could not be
determined at the time,
seemed to have lost
a piece of its long arm.
This first characteristic
chromosome change
in the human malignancy
soon designated
"Philadelphia chromosome"
after the city where it
had been discovered,
immediately provided
a very strong support
for the idea that
chromosome aberrations
indeed may play a major role
in the initiation of the
carcinogenic process.
This seemed to be
the true verification
of Boveri's somatic mutation theory.
It was reasonable to assume
that the acquired specific
chromosomal abnormality,
a perfect example
of a somatic mutation
in hematopoietic
bone marrow cell
or stem cell
was the direct cause
of the neoplastic state.
The discovery of the
Philadelphia chromosome
greatly stimulated interest
in cancer cytogenetics
in the 1960s.
But the results obtained
for more than 10 years
were quite disappointing.
Chromosomal abnormalities
were indeed found in most tumors,
but no new specific aberration
comparable to the
Philadelphia chromosome
was detected.
The aberrations that were
found varied among patients
with the same tumor types.
And so at the end of the 1960s,
most scientists agreed that
chromosomal abnormalities
were secondary epiphenomena,
not the cause,
but the consequence
of neoplasia.
The Philadelphia chromosome
seemed to be the
exception to the rule
that chromosome change
did not play any
important pathogenetic role
in carcinogenesis.
And as a result,
the interest in cancer cytogenetics
gradually faded away.
