Why do some cancers only affect young women? Scientists from UNIGE and the University Hospitals of Geneva (HUG) show that rare ovarian and pancreatic cancers in young women are caused by cells that have settled in an organ other than the one for which they were designed during embryogenesis. This deciphering of a migration of primordial germ cells in the human embryo will not change the surgical treatment of these patients, but leads to thinking about chemotherapy protocols and tending towards a more personalized oncology.
Mucinous tumors – cancer in which the tumor cells produce mucus – of the ovary and pancreas affect young women, aged 30 to 40 years. These tumors take the form of a large cyst, a kind of ball filled with fluid. They represent approximately 3% of ovarian and pancreatic cancers and are generally treated surgically. Taken in time, the cancerous cyst is completely removed. However, in 15% of cases, the cyst breaks before surgery; cancer cells spread giving rise to metastases highly resistant to chemotherapy. In this case, the prognosis for survival of patients usually does not exceed one year.
But what is the link between the ovary and the pancreas?Why is a non-gynecological cancer almost exclusively female? Indeed, among several forms of pancreatic cancer, one of them specifically affects women and often young women. How is this possible, even if the pancreas is an organ with little exposure to sex hormones? This pancreatic cancer, called a "mucinous cyst", has uncanny similarities to another mucinous cancer affecting the ovaries. By large-scale analysis of genomic data, researchers from Geneva in collaboration with colleagues from the United States, provide a first answer: these 2 tumors arise from embryonic germ cells. Although undifferentiated, these cells migrate to the reproductive organs. "It's only during embryogenesis that these organs are really close together," says the lead author, Dr. Labidi-Galy: At the very beginning of pregnancy, the embryo has primordial germ cells, in a way precursors of gametes, oocytes or spermatozoa, which, between 4 and 6 weeks of pregnancy undertake a long migration in the human body. They pass behind the future pancreas and arrive around the gonads, around the 7th week of pregnancy.
The transcriptomic profile of mucinous tumors is very close to that of germ cellscells: here the team develops a transcriptomic profile that defines the expression levels of the genes of primordial germ cells at the age of 6 years. 7, 11, 16 and 17 weeks of pregnancy, as well as healthy and tumorous ovarian and pancreatic cells. The researchers compare these data, on the one hand for the pancreas and, on the other hand, the ovary, by looking, for each of these two organs, at the profile of healthy tissues, mucinous tumors and other types of tumours. The results of the analysis are clear: in both cases, the transcriptomic profile of the mucinous tumor is far from the supposed tissue of origin (ovary or pancreas), but very close to the primordial germ cells. This suggests that these tumors are closer to the primordial germ cells than to the
The hypothesis is that some of these germ cells stop on the way , and by mistake in other organs, leading to a risk of tumors that can occur up to 30 years later. We found the same genetic mutations, the same types of victims – young women, often smokers – and, even more surprisingly, ovarian tissue in pancreatic cysts, the researchers point out. These clinical observations indicate that an arrest in cell migration that occurred accidentally during the embryonic life of these women could, decades later, be expressed by cancer, and this depending on other risk factors (such as smoking ) and also depending on where these primordial germ cells have settled.
Results that will not modify the surgical treatment of these tumours, but make people think about better targeted chemotherapy protocols.