Lymphoma development in Sjogren's syndrome - Novel p53 mutations

Objective, Sjogren's syndrome (SS) is a chronic autoimmune disease characte rized by lymphocytic infiltrations of the exocrine glands. Disease progress ion may lead to uncontrolled clonal proliferation of B lymphocytes and deve lopment of lymphoma. This study was undertaken to examine the possible invo lvement of the cell cycle checkpoint genes p53 and p21 in the pathophysiolo gy of the syndrome. Methods. Protein expression of p53 and p21 was studied, by immunohistochemi stry and Western blot analysis, in minor salivary gland (MSG) biopsy specim ens from 7 patients with SS and 5 control subjects. In addition, sequence a nalysis of the p53 gene was performed on DNA samples obtained from MSG biop sy samples of the same 7 patients with SS and from 4 patients with SS and i n situ non-Hodgkin's lymphoma (NHL). Results, The study revealed increased protein expression of p53 and p21 in MSG biopsy specimens from patients as compared with controls, while sequenc e analysis showed that the p53 gene was of the wild type, Furthermore, sequ ence analysis of the p53 gene from patients with SS and in situ NHL reveale d 2 novel mutations in exon 5 of the p53 gene. These mutations are single-b ase substitutions and appear to be functional since exon 5 is included in t he coding region of the p53 gene, Conclusion. This is the first report on wild-type p53 gene activation in SS , Our findings indicate a probable role for the DNA damage response genes i n the pathogenesis of this syndrome. The novel mutations of the p53 gene im plicate dysregulation of this tumor suppressor gene as a possible mechanism for lymphoma development in SS.