The Cancer Genome Atlas has reported results from its
first comprehensive study, which
focused on the deadly brain cancer glioblastoma. The
findings are reported in the Sept. 4 advance
edition of Nature.
The Cancer Genome Atlas team, comprising more than 100
investigators from seven cancer
centers and research institutions throughout the country,
analyzed 601 genes in tumor samples from
91 glioblastoma multiforme patients.
Investigators at the Johns Hopkins Kimmel Cancer
Center and University of Southern
California, members of the TCGA team, studied 2000
genes.
They reported findings on the MGMT gene, first linked
to glioblastoma multiforme, or GBM, in
1998 by Johns Hopkins investigators who found it was
altered by a cellular process known as
methylation. In 2002, they discovered that the gene
alteration makes brain cancer cells more
responsive to anticancer drugs known as alkylating
agents.
While brain cancer patients with the MGMT alteration
respond better to the commonly used
alkylating agent temozolomide, the new TCGA research found
that treatment also appears to cause
mutations in other genes, known as mismatch repair genes,
essential to DNA repair. These mutations,
they believe, lead to recurrence of the cancer, and these
recurrent tumors contain unusually high
numbers of gene mutations, making them resistant to
treatment.
The investigators stress that treatment with
temozolomide and radiation therapy is still the
most effective therapy for glioblastoma patients.
"These current findings should help us devise new
therapies that minimize the role MGMT plays
in cancer recurrence," said Stephen Baylin, deputy director
of the
Johns Hopkins Kimmel Cancer
Center and director of this portion of the TCGA
study.
Brain cancer affects more than 21,000 people in the
United States each year. GBM is the most
common and lethal form of brain cancer, with most patients
surviving just 14 months from the time of
diagnosis.
The TCGA is funded by the National Cancer Institute
and National Human Genome Research
Institute. The program began in 2006 to accelerate
understanding of the molecular basis of cancer
through full-scale, systematic studies of the human gene
changes involved in all types of cancer. GBM
is the first cancer studied under the program. A report of
the complete findings from the study can
be found on the National Cancer Institute's Web site,
www.cancer .gov.
"This type of comprehensive, coordinated analysis of
unprecedented multidimensional data is
made possible by advanced technologies utilized by teams of
scientists driven to solve complex
questions," said NCI director John E. Niederhuber in an NIH
statement. "It will now fall to a
dedicated cadre of laboratory scientists to turn this
important information into new life-saving
therapies and diagnostics for cancer."
The TCGA data are available to the research community
through a database at
cancergenome.nih.gov/dataportal.
Findings from a complementary but independent genomic
study of GBM by Johns Hopkins
Kimmel Cancer investigators are published in the Sept. 5
issue of Science Express.
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