Five reports present evidence that between 40% and 90% of colorectal cancers have reduced MGMT expression due to methylation of the MGMT promoter region.Similarly, out of 119 cases of mismatch repair-deficient colorectal cancers that lacked DNA repair gene PMS2 expression, PMS2 was deficient in 6 due to mutations in the PMS2 gene, while in 103 cases PMS2 expression was deficient because its pairing partner MLH1 was repressed due to promoter methylation (PMS2 protein is unstable in the absence of MLH1). In the other 10 cases, loss of PMS2 expression was likely due to epigenetic overexpression of the microRNA, miR-155, which down-regulates MLH1.In further examples, epigenetic defects were found at frequencies of between 13%-100% for the DNA repair genes BRCA1, WRN, FANCB, FANCF, MGMT, MLH1, MSH2, MSH4, ERCC1, XPF, NEIL1 and ATM. These epigenetic defects occurred in various cancers (e.g. breast, ovarian, colorectal and head and neck). Two or three deficiencies in expression of ERCC1, XPF or PMS2 occur simultaneously in the majority of the 49 colon cancers evaluated by Facista et al. Epigenetic alterations causing reduced expression of DNA repair genes is shown in a central box at the third level from the top of the figure in this section, and the consequent DNA repair deficiency is shown at the fourth level. When expression of DNA repair genes is reduced, DNA damages accumulate in cells at a higher than normal level, and these excess damages cause increased frequencies of mutation or epimutation.
Without proper treatment a permanent deformity of the finger may occur. Diagnosis
The diagnosis is generally based on symptoms and supported by X-rays. The injury can be accompanied by swelling and ecchymosis. Treatment
The management goal is to restore extension of the joint. Treatment is generally with a splint that holds the first joint of the finger straight continuously for 8 weeks. This should begin within a week of the injury. The splint may be worn just at night for a few additional weeks after this. The splint acts to immobilize flexing of the joint. Surgery generally does not improve outcomes. It may be required if the finger cannot be straightened by pushing on it or the break has pulled off more than 30% of the joint surface. Surgery may be preferred over the use of a split if a child is non-compliant. If the problem has been present a long time surgery may also be required. An open fracture may be another reason. Surgery will put the finger in a neutral position and drill a wire through the distal interphalangeal joint (DIP) to the proximal interphalangeal joint (PIP), forcing immobilization. See also
Busch fracture
Jersey finger

References


== External links ==