When this gene fails, cancer may follow

JOHNS HOPKINS (US) — A previously obscure gene plays a subtle but important role in regulating cell division and, when it fails, may help cause many types of cancer.

Researchers say the gene, known as FAM190A, allows cells to complete the final step in mitosis, the process in which a mother cell copies its DNA into a second nucleus and then divides into two genetically identical daughter cells.

In both cancerous and non-cancer cells, those lacking FAM190A often have difficulty separating. That results in abnormal single cells with two or more nuclei rather than pairs of daughter cells with one nucleus apiece.


“These cells try to divide, and it looks like they succeed, except they wind up with a strand that connects them,” says Scott Kern, professor of oncology and pathology at the Johns Hopkins University School of Medicine’s Kimmel Cancer Center.

“The next time (the FAM190A-lacking cells) try to divide, all the nuclei come together, and they try to make four cells instead of two,” Kern says. “Subsequently, they try to make eight cells, and so on.”

The study is published online in the American Journal of Pathology, nearly a century after German scientist Theodor Boveri linked abnormal mitosis to cancer. Until now, there had been no common genetic problem identified as the culprit in cancer-linked mitosis.

Kern’s group previously reported that mutations in FAM190A could be found in nearly 40 percent of human cancers. That report, published in 2011 in the journal Oncotarget, and the current one are believed to be the only published papers focused solely on FAM190A, whose function has been unknown.

Alterations in FAM190A may turn out to be the third most common in human cancers, after those for the more well-known genes p53 and p16, Kern says.

Researchers believe that FAM190A is important to survival in animal species and that severe defects in the gene therefore aren’t easily passed down from generation to generation. An animal with a severe mutation is more likely to die than to reproduce.

“The mutations seen here are very special. They don’t take out the whole gene but instead remove an internal portion and leave what we call the reading frame,” Kern says. “We think we’re finding a more subtle defect in human cancers, in which mitosis defects can occur episodically, and we propose it may happen in about 40 percent of human cancers.”

Kern says he plans to study FAM190A further by creating lab models of defects subtle enough for human cancer cells to survive. The research has been supported by the National Institutes of Health and by the Everett and Marjorie Kovler Professorship in Pancreas Cancer Research.

Source: Johns Hopkins University