What Does Breast Cancer Have to Do With Skin Stem Cells?

BRCA1 is a gene that plays a huge role in breast cancer. Particular mutations in BRCA1 predispose women increased risks of breast cancer cervical, uterine, pancreatic, and colon cancer and men to increased risks of pancreatic cancer, testicular cancer, and early-onset prostate cancer.

BRCA1 encodes a protein that helps repair damage to chromosomes. When this protein product does not function properly, cells cannot properly repair acquired chromosomal damage, and they die or become transformed into cancer cells.

What does this have to do with stem cells? A study led by Cédric Blanpain from the Université libre de Bruxelles showed that BRCA1 is critical for the maintenance of hair follicle stem cells.

Peggy Sotiropoulou and her colleagues in Blanpain’s laboratory showed that when BRCA1 is deleted, hair follicle cells how very high levels of DNA damage and cell death. This accumulated DNA damaged drives the follicle stem cells to divide furiously until they burn themselves out. This is in contrast to the other stem cell populations in the skin, particularly those in the sebaceous glands and epidermis, which are maintained and seem unaffected by deletion of BRCA1.

Sotiropoulou said of these results: “We were very surprised to see that distinct types of cells residing within the same tissue may exhibit such profoundly different responses to the deletion of the same crucial gene for DNA repair.”

This work provides some of the first clues about how DNA repair mechanisms in different types of adult stem cells are employed at different stages of stem cells activation. Blanpain and his group is determining if other stem cells in the body are also affected by the loss of BRCA1. These results might elucidate why mutations in BRCA1 causes cancer in the breast and ovaries, but not in other tissues.

Myriad Genetics Hordes Breast Cancer Data

Kathleen Sloan the president of the National Organization of Women has a troubling article at the Center for Bioethics and Culture website. It tells the story of a biotechnology company called Myriad Genetics and it BRCA1 & 2 test.

What the heck is BRCA1 & 2?  BRCA stands for “breast cancer” and mutations in BRCA 1 or 2 predispose females to breast and ovarian cancer. Mutations in BRCA genes also increase the risk of colon, prostate and pancreatic cancer.  Approximately 7% of breast cancer and 11 – 15% of ovarian cancer cases are caused by mutations in the BRCA genes.  If someone carries a mutation in either BRCA 1 or 2, they have a syndrome called Hereditary Breast and Ovarian Cancer (HBOC) syndrome.

The BRCA genes encode proteins that help repair DNA when it is damaged. Even though BRCA 1 & 2 work with several other proteins to accomplish this repair, mutations in the BRCA genes that compromise the quality of the proteins they encode can diminish the ability of cells to repair their DNA. Loss of efficient DNA repair systems leads to greater numbers of mutations in cells, some of which cause either loss of tumor suppress genes that normally put the brakes of cell proliferation, or activation of proto-oncogenes, which encode proteins that promote cell proliferation. Loss of tumor suppressor genes and activation of proto-oncogenes produces a cancer cell, and mutations in BRCA 1 or 2 and accelerate the onset of cancer cell formation (this is a highly simplified explanation and I apologize to the aficionados out there, but I am trying put the cookies on a nice low shelf).

Myriad Genetics came along and developed a genetic test for cancer-causing mutations in BRCA 1 & 2. This is good news, but Myriad Genetics is presently with holding their data from patients. This is not good news. Myriad Genetics wants to generate a database of mutations found in BRCA 1 and 2 genes from women all over the world. Some of these mutations do not affect the function of the encoded protein and do not predispose the patient to breast cancer, but some do. Which ones are harmful and which ones are not?

At this point things get sticky. Myriad has complied its sequence data on BRCA in order to construct a “variants of unknown significance” or VUS. Such a compilation would be invaluable, since it would help physicians correctly interpret the results of a breast cancer test. According to its present data archive, Myriad Genetics claims that only 3% of its tests fall into the VUS unknown category. However, other testing services report a 20% VUS rate. Who’s right? hard to say, given that Myriad Genetics will not release its data. Apparently they feel that their data has commercial value.

The problem is that lots of outfits that provided data to Myriad Genetics free of charge in order for them to develop their test. These other outfits have all their data available on public databases. What about Myriad Genetics – nope.

According to Ms. Sloan, “Myriad Genetics, producer of the world’s biggest-selling gene test for breast and ovarian cancers, has become synonymous with corporate greed. In an egregious breach of bioethics, the company refuses to share groundbreaking knowledge that could benefit cancer patients.”

Myriad worked hard to develop this test – I do not think anyone is contesting that. Myriad Genetics has every right to make money off their test, but when they start hoarding potentially life-saving data, I think Ms. Sloan is right that they have crossed the line.

Myriad Genetics is also being sued because of their attempts to patent the BRCA genes. An impressive consortium of researchers, genetic counselors, women patients, cancer survivors, breast cancer and women’s health groups, and scientific associations representing 150,000 geneticists, pathologists and laboratory professionals are all plaintiffs in this lawsuit against the U.S. Patent Office, Myriad Genetics and the University of Utah Research Foundation, which hold the patents on the genes.

The lawsuit avers that patents on human genes violate the First Amendment because genes are “products of nature.” Therefore, such things cannot be patented. Such an argument has a strong intuitive appeal, and is almost certainly correct.

Read Ms. Sloan’s article here and see what you think.