Young and Deadly: Cancer shares gene activity with developing lungs

Genes flipped on or off in developing mouse lungs have similar activity in human-lung cancers, say researchers. The finding hints at new ways to treat lung cancer, the leading cause of cancer deaths worldwide.

For more than a century, researchers have observed that the cells that make up many cancerous tumors look and behave much like immature cells in an animal fetus or a newborn. For example, tumor cells in lungs, brains, and blood typically have shapes, sizes, and quick-growth patterns similar to those of healthy cells in developing animals.

“We’ve often thought that [cancer cells] don’t become fully mature, that they’re somehow stuck in an early stage,” says cancer researcher Alvin Kho of Children’s Hospital in Boston.

Despite such a long history of suspicion, notes Kho, scientists knew little about whether the similarities between cancer and development exist at the genetic level.

To investigate, he and his colleagues mined databases that held information about which genes were turned on or off in tumors removed from 186 lung cancer patients and in 17 samples of lung tissue from healthy people. The researchers then compared this information with that in another database that records gene activity, or expression, in mouse lungs at points of development ranging from embryonic day 12 to 21 days after birth.

Examining 3,590 genes that people and mice share, Kho and his colleagues found 596 genes with similarly altered patterns of activity in lung tumors and during lung development. When the researchers looked individually at four different subtypes of lung cancer ranging from most to least aggressive—small-cell, squamous cell, adenocarcinoma, and carcinoid—they discovered that gene expression in these cancers line up along a developmental continuum. The more aggressive a subtype, the more closely its gene expression matches that of early lung development.

Taking the research a step further, Kho’s team looked at patient-survival records that accompanied the gene-expression data for just one subtype, adenocarcinoma. The scientists found that the closer a patient’s tumors matched early stages of lung development the deadlier the cancer proved to be. The researchers report their results in the July PLoS Medicine.

“These are interesting and important observations which reinforce previous reports” on cancer and developing tissues’ similarities, says cancer researcher David J. Sugarbaker of Harvard Medical School in Boston. He notes that developmental biologists are gradually amassing clues to the wide variety of chemical signals that prompt immature cells to become adult cells.

“If we can understand how primitive cells in the embryo differentiate into those of an adult organism, we can study those mechanisms as a way to potentially turn malignant cancers into more differentiated, nonthreatening cells,” Sugarbaker says.

He adds that doctors currently judge which subtype a cancer belongs to and how advanced it is by examining tumor cells under the microscope—a method that doesn’t always produce the most accurate results. Examining a tumor cell’s genes rather than its appearance could eventually take a doctor’s guesswork out of the picture, he says.

“I foresee a day when genetic signatures are what we talk about, rather than microscopic appearances,” Sugarbaker says.