Vengoechea J, Tallo C. “A germline deletion of 9p21.3 presenting as familial melanoma, astrocytoma and breast cancer: clinical and genetic counselling challenges”. J. Med. Genet. 2017, v. 54, 682-684.
Chan AK, Han SJ, Choy W et al. “Familial melanoma-astrocytoma syndrome: synchronous diffuse astrocytoma and pleomorphic xanthoastrocytoma in a patient with germline CDKN2A/B deletion and a significant family history”. Clin. Neuropathology 2017, v. 36, 213-221.
The 9p21.3 region contains three tumor suppressor genes – CDKN2A, CDKN2B and MTAP. Tumor suppressor genes are important because, as their name suggests, they help prevent tumors from developing in the body.
Therefore, deletions in tumor suppressor genes make an individual more prone to developing tumors and cancer. And indeed deletions in the 9p21.3 region of chromosome 9 are primarily associated with cancer predisposition and tumor development, including breast cancer, prostate cancer, melanoma, and leukemia.
Both articles report deletions within this region, and associate it with familial melanoma-astrocytoma syndrome (MAS). MAS is a rare, heritable disease that involves a predisposition to melanoma (tumors associated with skin cancer) and brain/spinal cord tumors (mainly, astrocytomas). MAS occurs with deletions in CDKN2A and CDKN2B; however, the exact mechanisms are unknown. This is because there are very few cases of MAS studied, and there is still much to discover about this disease. These articles help to further describe the characteristics of a deletion in the 9p21.3 region: which types of tumors can occur, life expectancy, and potential options for treatment.
The Vengoechea’s and Tallo’s article reports on a family with a 9p21.3 germline mutation that encompasses 9 genes within this region, including CDKN2A , CDKN2B and MTAP. The members of this family have a number of complications from the loss of these genes. These complications include melanoma, astrocytomas, leukemia, neurofibromas, and breast cancer to name a few. Lifespan varied drastically between members of the family. For example, one member was reported as 77 years old and had neurofibromas. However, two of her three children died at ages 34 and 7, from astrocytomas and leukemia, respectively. Since this deletion region involves multiple tumor suppressor genes, it is difficult to determine which ones are contributing to which diseases.
The Chan’s et al. article goes into more detail about MAS and its relationship with the CDKN2A and CDKN2B genes. In particular, the article reports the case if a 23-year old man with a germline deletion in the CDKN2A and CDKN2B genes. His family medical history includes cases of melanoma, glioblastoma, and oral squamous cell carcinoma. The patient himself had the following history of tumors: pleomorphic xanthoastrocytoma (anastrocytoma that occurs most frequently in children), diffuse astrocytoma (an astrocytoma without well-defined borders), and a mass with the potential to develop into a peripheral nerve sheath tumor (a tumor of the connecting tissue that surrounds nerves). The results from the study of this patient reveal more about the diversity in tumor types in individuals with MAS. Astrocytoma can refer to a vast range of tumors in individuals, as seen in the fact that the patient had both a pleomorphic xanthoastrocytoma and a diffuse astrocytoma.
Ideal treatment options for patients with MAS are unknown. However, the Chan’s et al. article does describe many preventive measures taken by patients to catch developing tumors before they become unmanageable. For example, patients require brain imaging (to monitor potential astrocytoma development), dermatological evaluations (to monitor potential melanoma development), dental exams (to monitor potential mucosal melanoma development), and body imaging (to monitor a number of other potential tumors). While laborious, until more is uncovered about this disease, continual monitoring of tumor development appears to be the best option.