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Molecular Pathology represents a major interface
area where molecular skills within The Institute of Cancer Research
are used to identify new diagnostic and prognostic markers that
can be used in the management of cancer patients within The Royal
Marsden NHS Trust. Molecular pathology studies have been carried
out for many cancer types with some of the most successful interactions
in the fields of breast cancer, sarcoma and leukaemia. These initiatives
are continuing but a major emphasis of future studies will be
on testicular and prostate cancer focused around the newly opened
Male Urological Cancer Research Centre. For many cancers the genes
involved in development remain to be isolated. This problem is
being addressed both by molecular cytogenetic and molecular cloning
projects within The Institute and by the Cancer Genome Project
that has recently been initiated by The Institute Scientists,
Professor Mike Stratton and Dr Richard Wooster. The aim of this
latter project is to identify new cancer genes through the systematic
screening of all genes in the human genome for mutations in cancer
cells. Once new genes have been identified they can, through the
expression or mutational screening of tumour sets, be assessed
for their use in cancer management. The Institute has also invested
in the setting up of a cDNA microarray laboratory. Correlation
of expression profiles determined using microarrays with clinical
outcome provides another method for identifying novel diagnostic
and prognostic markers. These approaches are particularly well
illustrated by the work currently being carried out in The Institute
Section of Molecular Carcinogenesis.
Section of Molecular Carcinogenesis, Male Urological
Cancer Research Centre, and Haddow Laboratories, The Institute,
Sutton
A major theme of the work of the Section is the
application of molecular biological technologies to clinical problems
that have been identified through our close links with The Royal
Marsden. Many of the genes that are involved in the development
of human cancer still remain to be isolated. We are, therefore,
using recombinant DNA technology to identify cancer-causing genes
(oncogenes) that are specifically activated in certain types of
solid tumours, such as sarcomas and cancer of the kidney, prostate
and testis, in the hope that their isolation will lead both to
the development of new methods of diagnosis and to improvements
in our understanding of the molecular mechanisms of tumour development.
We are also developing approaches utilising microarray technology
that should lead to the identification of new markers that can
be used in the clinical management of cancer. It remains a disturbing
fact that the environmental and dietary agents that may be responsible
for many of the major types of human cancer (eg cancer of the
colon and breast) have still to be identified. Accordingly, one
of our major objectives is to use a highly sensitive technique
called 32P-postlabelling to identify new classes of
chemicals that react with DNA in human tissue and which, therefore,
may contribute to cancer development.
Highlights of 2000
- The discovery in Dr Goodwin’s and Professor
Cooper’s groups that the PRCC protein involved in kidney cancer
development is a component of the pre-mRNA splicing complex.
- The identification in Professor Cooper’s and
Dr Wooster’s groups of several new candidate oncogenes that
may be involved in the development of human breast cancer.
- The discovery in Professor Phillips’ group
that human prostate tissue can metabolically activate carcinogens
present in cooked meat, a process that could contribute to prostate
cancer development.
- The development in Dr Shipley’s laboratory
of a novel technique called CESH for mapping gene expression
in human cancer.
Future Aims
Key future aims of this Section are:
- to investigate the possible role that DNA damaging
agents found in normal breast tissue may play in the aetiology
of breast cancer;
- to apply microarray technology to the identification
of new cancer genes and genes that may represent useful markers
in the clinical management of cancer;
- to investigate the normal function of cancer
genes that have been isolated by the Section.
Phd Studentship available
Identification of predictors of prostate cancer
behaviour using DNA microarrays (more
details)
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Last Modified 31/1/02
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