Breast Cancer Study Finds Particular Cell Type Especially Vulnerable To Turning Cancerous

New research shows that a specific type of cell in the breast seems especially genetically vulnerable to turning into cancer. The finding points to a possible new way of gauging a woman’s breast cancer risk, even if she doesn’t have the characteristic BRCA mutation that prompted Angelina Jolie’s preventative mastectomy.

The secret lies in DNA, but not necessarily in your genes. The chromosomes that make up a person’s genome are capped with regions called telomeres, which contain a long string of repeated short DNA sequences that help keep your genes stable. Cell division shortens chromosomes slightly, so without the buffer of a telomere, a person’s genome would increasingly degrade with each cell division. Shorter telomeres are a characteristic feature of many cancer cells – though scientists still aren’t quite sure why. (Normally, a cell with extremely short telomeres would start cannibalizing its own genome as it divided, but cancer cells have found a way around this by turning on enzymes that replenish the ends.)

Now, scientists from Indiana University School of Medicine and the British Columbia Cancer Agency’s Terry Fox Laboratory have found that a certain kind of breast cell called a luminal progenitor tends to have very short telomeres as well as high levels of DNA damage. Their results were published in the journal Stem Cell Reports on Tuesday.

"This is the first report of a particular normal human precursor cell type that shows such telomere malfunction," Connie Eaves, a researcher with the British Columbia Cancer Agency, said in a statement Tuesday. "The luminal progenitors we have found to possess this feature are thus now being brought into the spotlight as a likely stage where breast cancer may 'take off.'"

Knowing that the luminal progenitor cells in the breast are particularly vulnerable to turning into cancer could lead to new ways to detect and treat breast cancer, as well as a new way to gauge a person’s risk for it. Whereas current breast cancer genetic tests look for specific mutations in the BRCA1 and BRCA2 genes, using shortened telomeres as a flag could be a boon for men and women that don't have BRCA mutations but could still develop cancer. According to Eaves, while it would be hard to detect short telomeres in specific cell types with a blood test, it might be possible one day to take biopsies of cells and examine them for dangerously short telomeres.

Meanwhile, Indiana University researcher David Gilley, a co-senior author with Eaves, says his lab is working on both blood and tissue tests to pinpoint critically short telomeres that result in a condition called a telomere fusion, which causes one chromosome to link up improperly with another chromosome.

“Telomere fusions are extremely toxic/nasty to the genome and probably are a major mechanism of genomic instability sparking cancer development,” Gilley wrote in an email.

Another possible approach in development at Georgetown University involves using a blood test to look for short telomeres on specific chromosomes. This is based on the work of Yun-Ling Zheng, who found an association between specific telomere deficiencies and a higher risk for breast cancer in younger women.

“If confirmed in future studies, chromosomal arm-specific telomeres are likely to be a useful panel of blood-based biomarkers for breast cancer risk assessment, given their strong associations with breast cancer risk,” Zheng and her colleagues wrote in the journal Human Molecular Genetics in 2011.

SOURCE: Kannan et al. “The Luminal Progenitor Compartment of the Normal Human Mammary Gland Constitutes a Unique Site of Telomere Dysfunction.” Stem Cell Reports published online 4 June 2013.