Mutated cancer gene traced to 1700s couple

University of Hawaii Cancer Center researchers investigating a mutated gene that causes different forms of cancers were confronted with a confounding mystery when they discovered the gene in four apparently unrelated families living in four different states.

One possible answer was that the families had sometime in the past passed through a hot spot for such mutations.

The other was that the families actually were related, unbeknownst to one another.

The implications were significant. The mutation to the BAP1 gene is known to cause mesothelioma, melanoma, renal carcinoma and other potentially fatal cancers.

Under the direction of the UH Cancer Center’s Michele Carbone, the team traveled across the United States and Europe looking for genealogical links between the families.

To identify families with the BAP1 cancer syndrome, the team screened patients with family histories of multiple mesotheliomas and melanomas and/or multiple cancers.

The expansive effort eventually yielded a common link: a couple that emigrated from Germany to America in the early 1700s.

The descendants of this couple branched into a family tree of about 80,000 people, Carbone said.

With the genetic lines that contain the BAP1 mutation having been identified, descendants of the couple can now be monitored, making early detection more likely.

“For some of the cancer types, this would be life saving,” Carbone said in a release. “Moreover, early detection of mesothelioma and of other cancers that develop in BAP1 carriers are associated with much better survival.”

The findings were published in the Dec. 18 issue of PLOS Genetics.