This is because up to 92% of NF cases have a specific type of fusion gene in their tumor cells. Fusion genes are abnormal and potentially tumor-inducing genes formed by mergers between parts of two different genes. The fusion gene involved in NF merges part of the USP6 gene to a part of any one of numerous other genes. The USP6 gene is responsible for producing ubiquitin carboxyl-terminal hydrolase 6a, a deubiquitinating enzyme that indirectly regulates various signaling pathways which regulate cell growth and death. All of the USP6-containing fusion genes overproduce a chimeric protein (i.e. an abnormal protein consisting of parts derived from different genes) with uncontrolled deubiquitinating enzyme activity that is thought to contribute to the development of NF. Presentation
Nodular fasciitis occurs in all age groups but more often affects 20-40 year old individuals. Males and females are equally affected. NF tumors, which may be tender or painful, typically present as rapidly growing solitary lesions that reach a final size (usually of 2–3 cm.) within a few weeks. They are located in the upper limbs (39–54% of cases), trunk (15–20% of cases), lower limbs (16–18% of cases), and head or neck area (20% of cases). (Involvement of the head or neck area is more commonly observed in children.) Rare cases off NF have occurred in the: 1) joints of the knee (18 cases), shoulder (3 cases), hand (3 cases), elbow (2 cases), hip (1 case), ankle (1 case), and temporomandibular joint (1 case); or 2) peripheral nerves of the arm (i.e.
Gene abnormalities
Until recently, nodular fasciitis was considered a reaction to trauma or some other unidentified insult at the site where the tumor subsequently developed. However, recent findings indicate that up to 92% of NF tumors involve the self-limiting growth of a clone (i.e. a group of identical cells that share a common ancestry} of neoplastic cells that contain a fusion gene. Fusion genes are abnormal genes consisting of parts from two different genes that form as a result of large scale gene mutations such as chromosomal translocations, interstitial deletions, or inversions. The fusion gene found in NF tumor cells consists of a part of the USP6 gene combined with any one of numerous other genes. Its most common partner gene in NF is the MYH9 (i.e. myosin-9) gene. This USP6-MYH9 fusion gene forms as a result of a translocation of part of the USP6 gene located at band 13.2 on the long (or "q") arm of chromosome 17 with part of the MYH9 gene at band 13.2 on the short (or "p") arm of chromosome 22. Other genes that partner with the USP6 gene to form a fusion gene found in NF include the: RRBP1 (i.e.