It’s hard to navigate without a map — and that not only goes for driving, but for our genetic landscape, too.
That’s why the government is supporting efforts by eight scientists nationwide to chart changes in cells’ DNA that are associated with cancer — and a City of Hope scientist is among those embarking on the mission.
The National Institutes of Health has awarded Gerd Pfeifer, Ph.D., professor and chair of the Division of Biology, $465,000 over two years. Pfeifer will catalogue deadly genetic changes linked to lung cancer.
Laboratories at institutions ranging from Johns Hopkins University to Stanford University received the grants as part of The Cancer Genome Atlas (TCGA) project, which aims to develop innovative technologies to detect and treat cancer.
Pfeifer’s grant was the largest of the eight awarded.
TCGA aims to identify every change in an individual’s DNA sequence associated with all types of cancer. When scientists can better take stock of these changes, they can also come up with new ideas for ways to target it or discover cancer early.
But charting these changes could take a whole decade, experts said. In the project’s pilot phase, investigators — including Pfeifer — will start the journey by focusing on genetic changes associated with lung, ovarian and brain cancers.
“Each of the dozens of types of cancer likely will have a different genomic profile or set of profiles,” said NHGRI Director Francis S. Collins, M.D., Ph.D., who previously directed the Human Genome Project and is known for his landmark discoveries in genetics. “We urgently need tools equal to this task. One of the major lessons we learned from the Human Genome Project is that technology development is essential for success.”
Pfeifer’s lab has historically focused on a way that DNA can be chemically changed — a process known as methylation — which can occur in cancer. One example is lung cancer.
“We look at DNA methylation in cancer cells, which in most cases is associated with gene silencing,” explained Pfeifer. “Methylation shuts down gene expression more or less permanently and these changes in cancer-relevant genes may lead to malignancy.”
As part of the project, Pfeifer will analyze several hundred human tissue samples that come from centralized tumor banks. They aim to not only catalogue methylation changes in the DNA of tumor cells, but also to greatly improve the sensitivity of detection tests, a technological advance needed to develop life-saving diagnostics.
“Currently we can do this type of analysis with 50,000 to 100,000 cancer cells,” Pfeifer said. “We want to bring this down to 1000 cells or less, because in precancerous lesions or specimens on microscope slides, you often have very few cells to look at.”
Devising better diagnostic methods to detect any genomic changes at early stages — whether they are changes in methylation “signatures” or DNA errors known as mutations — is an acute need in lung cancer, which often shows no symptoms. As a result, lung cancer often has reached advanced stages by the time it shows up on imaging scans.
“We have technologies to determine risk factors for other cancers, such as mammography and PSA tests,” said Pfeifer, referring to tests for breast and prostate cancer. “This is a major reason the five-year survival rate for these cancers is more than 80 percent. But for lung cancer, the survival rate is dismal — maybe 15 percent — because it cannot be detected early.”
When completed, the TGCA project will establish a publicly available, online catalogue, or “atlas,” listing every mutation associated with cancer. Any researcher could then refer to the atlas in devising novel drug therapies or diagnostic tests.
For more details about The Cancer Genome Atlas, go to http://cancergenome.nih.gov.
