COLLECTION OF DNA AND RNA FROM BREAST CANCER PATIENTS

All cancers arise due to accumulation of damage in genetic material which
affects critical target genes. Altering the
function of these critical genes affects growth control in cells resulting in
what is clinically recognised as cancer.
Identifying the specific abnormalities and genes associated with a particular
cancer allows a greater understanding of the
causation of the cancer and potentially provides targets for diagnostic
investigations and novel anti*cancer therapies.
Important examples of the latter include Herceptin in breast cancer, Gleevec in
chronic myelogenous leukemia and
Iressa/Tarceva in non*small cell lung cancers.
The Cancer Genome Project at the Sanger Institute was established to undertake
systematic genomic analyses of cancers
in order to identify of new cancer genes. Subsequently, there has been a major
effort to organise and coordinate
international efforts by establishment of the the International Cancer Genome
Consortium, whose goal is to more fully
investigate the many different types of human cancer * ultimately leading to
complete cataloguing of all genetic events that
are important in the cancer. These data will be the foundation for further
efforts focused on improving prevention,
diagnosis and treatment informed by detailed molecular knowledge of the key
events contributing to each tumour type.
Following the completion of the human genome reference sequence, the
possibility of using systematic genome wide
screens to help understand the mechanisms of cancer development and biology is
now a realistic goal. As a result the
International Cancer Genome Consortium was launched to maximise the impact and
aid co*ordination of such studies.
The principle aim of this study is to characterise all of the genetic
alterations that are present in different types of breast
cancer by comparing the cancer genome to it's matched normal genome.
Somatic mutations refer to changes in the DNA sequence of an individual's cells
that occur during normal life. They are
not inherited from parents or passed onto offspring. However, if one or more of
these changes takes place within or affect
a particular type of gene (known as a cancer gene) then the cell that has
acquired the change will proceed to become a
cancer cell. Understanding the critical mutational events underlying the
development of cancer is paramount for
advancing prevention, early detection and effective treatment of the disease.
Proteins in the body are not made from DNA directly. An edited version of DNA
is produced which is known as RNA.
The process of making RNA is termed transcription and the RNA acts as the
intermediate between DNA and the rest of
the cell. The transcriptome is the complete set of RNA products that are
produced by the genome. Transcriptomics
refers to the study of these RNA products. Epigenetic processes control normal
growth and development by activating or
deactivating certain genes within a cell. Epigenomic data sets will provide
information relating to any changes in those
processes across many genes or an entire organism.
Study of the whole genome to identify mutational changes which may influence or
give rise to the development of cancer
will include in*depth sequencing of DNA as well as studying the transcriptomes
and epigenomes to understand the
processes occuring in tumour cells when compared to normal cells.

The principle aim of this study is to characterise all of the genetic
alterations that are present in different types of breast
cancer by comparing the cancer genome to it's matched normal genome.The primary
goals of this ICGC project, which focuses on breast cancer, are:
1) Co*ordinated generation of comprehensive catalogues of genomic abnormalities
(somatic mutations) in breast cancer
to include single*nucleotide variants, insertions, deletions, copy number
changes, translocations and other chromosomal
rearrangements by sequencing of cancer and matching normal genomes to high
levels of coverage.
2) Generate complementary catalogues of transcriptomic and epigenomic data sets
from the same tumours.
(Some of this work may be carried out by one or more of the international
partners in the Breast Cancer Working Group
and not necessarily at the Sanger Institute).
3) Release the data to the research community as rapidly as possible and, where
appropriate, with minimal restrictions to
accelerate research into the causes and control of cancer.

Purpose:
To identify the full range of genomic abnormalities that can lead to the
development of cancer.
Design:
From the tissues removed from participants for routine diagnostic purposes as
part of their clinical care, DNA and RNA will
be extracted. At the point of clinical care, a microfine section of the tissue
that has been removed will be used to create a microscopic slide for review by
pathologists. These slides will also be made available for this study and as
such may be stored at the Wellcome Trust Sanger Institute for a period of time.
Tumour DNA will be analysed and compared to matching constitutional (normal)
DNA from the same patient to identify
tumour*acquired (somatic) alterations. These alterations (mutations, copy
number alterations, translocations and other
genomic aberrations) will be identified in multiple tumours and then these sets
compared against each other to determine
which genes are mutated in common and which pathways have been targeted. A
combination of DNA sequencing,
methylation, epigenetic and microarray*based methods will be used in these
analyses.
The sequencing will consist of next*generation deep sequencing of the tumour
nucleic acids at the Wellcome Trust
Sanger Insitute which will identify the variants present in the tumour down to
single nucleotide resolution. It is possible that
a subset of sequencing maybe carried out at Illumina, Inc based at Great
Chesterford, Cambridge. In additional, normal
DNA extracted from blood (or other non*cancerous tissue biopsy samples) will be
sequenced at sufficient coverage to
allow true somatic variants to be initially identified and separated from
previously undescribed population polymorphisms.
Reconfirmation of novel somatic variants (i.e. those present in the tumour but
not the normal DNA) will be conducted by
resequencing of the specific regions

not applicable