HeLa genome offers clues to cells’ cancerous nature

A detailed DNA profile of the world’s most widely used cancer cell line sheds light on the genetic chaos the cells use to grow virtually unchecked in laboratory cultures. That property may also explain their virulent growth in the woman who unwittingly left them to science.

The famous cells came from a biopsy taken in 1951, when Henrietta Lacks was dying from cervical cancer at Johns Hopkins Hospital. Although no one asked Lacks or her family for permission to perform experiments with the cells, they formed the first immortal human cell line ever successfully grown in the lab. HeLa cells were pivotal in developing a vaccine for polio, among other scientific milestones.

But one problem for researchers using HeLa cells has been that their genome is a scrambled version of a normal human genome. This makes it more difficult to design and interpret experiments using the cells.

The new work, reported by University of Washington researchers in the Aug. 8 Nature, will help scientists make better use of HeLa cells by providing information on the arrangement of genetic variants on chromosomes.

These details were “long overdue,” says Peter Park, a computational biologist at Harvard Medical School. “We no longer have to make assumptions about what the HeLa genome looks like.”

Human cells normally have two copies of each chromosome. Sometimes, a genetic variant differs between the two copies. But standard sequencing methods mix the data together, so it’s impossible to figure out which variant is on which chromosome. The University of Washington group overcame that obstacle by using a method that identifies which variants sit together on the same chromosome.

This new level of detail helps reconstruct an event that is thought to have contributed to Lacks’ cells becoming cancerous. Scientists already knew that the HeLa genome contained human papillomavirus DNA, which comes from the genome-invading virus that causes nearly all cervical cancers. The virus DNA had embedded itself near MYC, a human gene that, when artificially switched on, can cause cells to become cancerous.

The new study found that in chromosomes with viral DNA, the MYC gene turned on. But in matching chromosomes without viral DNA, MYC was not active. That meant that the viral DNA probably turns the MYC gene on, but only within the same chromosome. The researchers also found that the viral DNA actually touched the MYC gene, suggesting it directly causes the different MYC activity on the chromosomes. This reveals one of the ways that the invading virus might have helped Lacks’ cancer cells to grow uncontrollably.

“It’s a really lovely piece of work,” says geneticist Daniel MacArthur of Massachusetts General Hospital. “It’s a shame that the technical achievements of the authors may be overshadowed by the ethical challenges.”

The HeLa genome sequence was published for the first time in March, by a research group led by Lars Steinmetz at the European Molecular Biology Laboratory in Heidelberg, Germany. These data, published in G3: Genes, Genomes, Genetics, mapped out the many rearrangements and mutations that distinguish the HeLa genome from a healthy human genome.

The study sparked a controversy because the sequence was freely available and could potentially be used to infer some of the genetic variants carried by Lacks’ family. In response the team withdrew the HeLa sequences from the public database.

The National Institutes of Health has now negotiated an agreement with the Lacks family that restricts access to HeLa genome and requires future publications based on the data to acknowledge the contribution of Henrietta Lacks and her family. The new arrangement also has members of the Lacks family joining a board that oversees requests to use the data.