ELIO Academy Logo
ELIO Academy Logo

Gynecologic Manifestations of the DICER1 Syndrome

By: Moumita Balakundhi, Diablo Vista Middle School

The DICER1 gene provides instructions for creating a protein that plays a role in regulating the activity of other genes. In addition, the DICER protein aids in producing a molecule called microRNA. MicroRNAs are short lengths of RNA, a single-stranded non-coding RNA fragment that prevents the production of a protein by binding and destroying the messenger RNA that would have produced the protein. This paper focuses on DICER1 syndrome. DICER1 syndrome, first identified in 2009, is a rare pediatric tumor syndrome caused by germline truncating mutations in the DICER1 gene, characterized by a spectrum of rare, primarily pediatric tumors. A germline mutation is when a single gene changes in a body’s reproductive cell, (sperm or egg) that becomes multiplicated into the DNA of every cell in the offspring’s body. This cell mutation is an inherited disorder that increases the risk of various cancerous, malignant, and benign tumors found in the lungs, kidneys, ovaries, and thyroid. Many of these mutations lead to a short DICER protein incapable of producing microRNA. Without regulation by miRNA, genes are activated abnormally, which could cause cells to grow and divide uncontrollably and lead to tumor formation. I chose this topic because I want to become an OB/GYN, and further sub-specialize in either oncology or maternal family medicine.

There is no known cure for DICER1 syndrome. Rather, the focus of medical care for most patients with DICER1 syndrome is cancer screening and surveillance to allow clinicians to discover tumors at their earliest, treatable phases. Treatment for patients that develop tumors is based on the site, stage, and type of the DICER1-associated tumors and may include: surgeries to remove the tumors or growths, chemotherapy, and radiation. Clinical presentation of DICER1 syndrome may include, cystic nephroma, ovarian Sertoli-Leydig cell tumor (SLCT), and multinodular goiter (MNG).

The DICER1 gene gives instructions to create proteins that produce molecules called microRNA. Through this role in regulating the activity of genes, the DICER protein is involved in multiple functions, including cell proliferation and cells taking on specialized functions. DICER1 syndrome is also associated with tumors in the ovaries called Sertoli-Leydig cell tumors, which generally affect women in their late teens or twenties. Occasionally Sertoli-Leydig cell tumors release male hormones, such as testosterone; in these cases, women may develop facial hair, a deep voice, a more prominent body, and other male markers. In addition, some affected women have irregular menstrual cycles. Sertoli-Leydig cell tumors usually do not metastasize. Patients with DICER1 syndrome who develop tumors most commonly develop pleuropulmonary blastoma, which is a tumor that grows in lung tissue or the outer covering of the lungs. Cystic nephroma, a benign fluid-filled cyst in the kidneys, can also occur.

A study on DICER1 syndrome consisted of 16 biologically related individuals. The study was conducted by the Institutional Review Board of the Faculty of Medicine of McGill University, and all procedures were performed in accord with the medicinal ethical criteria of the Helsinki Declaration. The complete sequencing of DICER1 in the proband’s germline DNA did not determine any mutations, small insertions, or deletions. (Proband means the person serving as the starting point for a genetic study of a family) However, the sequencing revealed loss for exons 23 and 24, resembling a deletion. The testing of fifteen family members revealed eight carriers of the deletion. All carriers had been diagnosed with MNG or SLCT (The proband had been diagnosed with both), except for two individuals aged 42 and 10. Two non-carriers had MNG, one focusing on differentiated thyroid cancer of the papillary subtype. One female non-carrier was diagnosed with breast fibroadenoma.

_ By: Moumita Balakundhi_ (External student, guest post on the request of Mentors)

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of Elio Academy.