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Inside Tract - Esophageal cancer: We know the genes

Inside Tract Spring 2012

Esophageal cancer: We know the genes

Date: March 1, 2012


Two new studies from Stephen Meltzer’s lab solidly advance ideas about genes and esophageal cancer. One of them—which has pinpointed the mutations—is poised for quick translation into personalized medicine.

Any understanding of esophageal adenocarcinoma is welcome, given that the disease is rising dramatically in the West and that a meager 15 percent of patients reach five-year survival.

“Now our progress will likely climb,” says molecular geneticist Meltzer, thanks in part to deep sequencing, a new technique “that tells us about all RNA molecules in a sample, not just those we know to look for.”

 Deep sequencing precisely identifies RNA while also quantifying the molecules—something no other automated method does. And that gives an unprecedented perspective on a tissue’s biochemical pathways. It draws what’s important to the surface.

 It also begs investigators to compare normal tissues with tumors and pathological stages in between. So Meltzer and collaborators have done just that. Using deep sequencing, they’ve noted what’s genetically turned on or off—and how much—in samples of healthy esophagus, pre-cancerous Barrett’s esophagus and frank adenocarcinoma.

Using the same platform, they’ve also surveyed the DNA for mutations in all 20,000 genes in patients’ genomes.

Results so far?

  • Meltzer’s team has found all of the genes that mutate in esophageal cancer and how frequently the mutations occur. This could expose new chemotherapy targets. As important, it’s a key step toward individualized medicine. “Within a few years,” says Meltzer, “we envision being able to tally a patient’s specific mutations and to select chemotherapies to target them.”
  • His team has become adept in molecular genetics’ current white-hot specialty, identifying long noncoding RNA molecules (lncRNA). Once lumped with “junk DNA” because it doesn’t code for proteins, lncRNA is unexpectedly common and appears to work behind the scenes to fine-tune various bio-processes ranging from development to cancer.

Recently, Meltzer’s lab found a wayward lncRNA in esophageal cancer that apparently acts like an oncogene to speed cell growth and invasion. The team’s been able to turn it off in human tumor cultures and shut down cancer-like activity.

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