| 60 61 | See page 67 for references MRE11A gene summary MRE11A-associated hereditary cancer Gene name MRE11A Associated syndrome MRE11A-associated hereditary cancer Primary associated cancers Breast, ovarian Frequency Unknown Inheritance pattern Autosomal dominant Overview · ·Cancer risks associated with MRE11A mutations are not fully understood; however, MRE11A may be associated with a moderate risk of breast and ovarian cancer. · ·Because MRE11A cancer risks are not fully understood and because mutations may not fully explain the cancer risk in a family, patients and their relatives may or may not benefit from this information. Additionally, family members who test negative for a known familial MRE11A mutation may still be at increased risk for cancer based on the family history. · ·Individuals who inherit an MRE11A mutation from both parents are at risk for ataxia telangiectasia-like disorder. For individuals who test positive for a mutation in MRE11A, it may be appropriate to consider carrier screening for MRE11A mutations in a spouse/partner. About MRE11A MRE11A is part of the MRN complex, which is formed by proteins encoded by MRE11A, RAD50, and NBN. The MRN complex plays a key role in DNA double-strand break repair, meiotic recombination, cell cycle checkpoints, and maintenance of telomeres, and interacts with several other proteins known to be associated with an increased risk of breast and/ or ovarian cancer, including BRCA1, ATM, and CHEK2. As such, mutations in MRE11A have recently been studied in association with breast and ovarian cancer; however, data remain limited. · ·Pituitary tumors: Develop in 15% - 55% of MEN1 mutation carriers. These tumors can impact a woman’s menstrual cycle, can cause sexual dysfunction in males, or can lead to an overproduction of growth hormone. · ·Gastro-entero-pancreatic (GEP) tract tumors: Develop in 40 % - 70% of MEN1 mutation carriers. These tumors have a high potential of becoming malignant and can also impair the functioning of the stomach and small intestines. · ·Other hormone-producing tumors such as adrenal cortical tumors and carcinoid tumors can also be observed in MEN1 mutation carriers. · ·Benign tumors of the skin (angiofibromas, lipomas, and collagenomas) and of the central nervous system (meningiomas and ependymomas) have also been reported in individuals with MEN1 mutations. Potential management options The most important aspect of management of individuals with a MEN1 mutation is increased screening to allow for earliest detection of any health concerns or potentially problematic tumor growth. · ·Clear guidelines exist for the management of the various tumor manifestations and their impact on the hormone levels in individuals who are identified to have a mutation in MEN1. It is recommended that MEN1-mutation carriers work with a multidisciplinary team, often led by an endocrinologist, to create an individualized management plan. Screening recommendations include regular blood tests and imaging (with MRI or CT scans) of specific organs like the brain, chest, and abdomen. · ·Given the impact of many of the tumors that can develop in these individuals, surgical management, including surgery of the parathyroid gland, and the use of targeted medication regimens are often recommended prior to onset of symptoms. · ·Screening recommendations for MEN1-mutation carriers may begin as early as age 5. Therefore, genetic testing should be considered for children in families with MEN1 mutations.