DNA sequence analysis of the p53 gene may provide information
about the response to therapy for breast cancer patients, according
to a study presented by Jonas Bergh, MD, associate professor of
oncology, at the annual meeting of the American Society of Clinical
Oncology. The study represents the first complete sequencing of
the p53 gene in a large retrospective study of a population based
cohort. Previous studies have focused primarily on exons 5, 6,
7, and 8, using techniques such as single strand conformation
polymorphism (SSCP) to screen for mutations, followed by sequencing
only to verify identified mutations. Since mutations are found
over the entire coding sequence, some could be missed using traditional
Mutations of the p53 gene are considered to be a critical step
in the development of human malignancies, including breast cancer.
These alterations can be determined using immunohistochemistry
techniques or DNA analysis, which can reveal prognostic information.
Conducted at the Uppsala Akademiska University Hospital in Sweden
in cooperation with Pharmacia Biotech's molecular systems division,
and the support of the Swedish Cancer Society, the study's objective
was to analyze the associations between mutations and outcome
using a cDNA sequencing technique. Further, the study was designed
to demonstrate the use of automated DNA sequencing of the complete
p53 gene to process large numbers of samples.
Frozen tumor material from a total of 317 consecutive Scandinavian
women, operated on for breast cancer from January 1987 through
December 1989, was analyzed by means of a complete cDNA sequencing
of the p53 gene and a total of 69 mutations were discovered.
97 patients had primary lymph node metastases while 206 were code
negative. In 14 cases, the node status of the patient was unknown,
since axillary exploration was not performed. The median follow
up time was 58 months.
Study findings demonstrated that mutations of the p53 gene identified
a group of patients with worse prognosis. The study also found
a correlation between the location of the p53 mutation and the
prognosis of node negative and node positive breast cancer patients.
As with other studies, these findings require review and verification
by the scientific community.