Study On Mutations Of The PTEN Gene In Diffuse Large B-cell Lymphoma

Introduction Diffuse large B-cell lyrnphoma(DLBCL) comprises a diverse spectrum of lymphoid neoplasms with heterogeneous histology, clinical features, treatment response, and prognosis. Survival can be predicted on basis of clinical characteristics, as International Prognostic Index (IPI) recently established by the International Non- Hodgkin抯 Lymphoma Prognostic Factors Project. However, the genetic and molecular basis of the progression of the disease and its response to therapy has yet to be elucidated. Deletion of the q23-24 region human chromosome 10 is one of the most frequent genetic alterations in non-Hodgkin抯 lymphoma (NHL), suggesting that inactivation of a tumor suppressor gene in this region is involved in the development or progression of this carcinoma. Recently, A new tumor suppressor PTEN has been identified from this chromosomal region. PTEN acts as a phospholipid phosphatase dephosphorylating the position D3 of the phosphatidylinositol 3,4,5- trisphosphate(PIP3). Mutations of this gene have been found in various advanced tumors and cell lines. Glioblastoma, malignant melanoma and endometrial carcinoma showed a high frequency of PTEN mutations. To our knowledge, there have been no reports of mutations of PTEN gene in DLBCL. Abstract Objective The aim of this study is to detect the mutations of PTEN and PTEN protein expression in diffuse large B-cell lymphoma (DLBCL) and whether PTEN play a role in the pathogenesis of NJ-IL. Both PTEN and p53 genes have be known to be related to the genetic control of apoptosis or programmed cell death. We tried to study the PTEN and p53 mutations and their protein expression, in relation to clinical presentation. response to therapy and survival of patients with diffuse large B- 7 ccli lymphoma and their relationship to International Prognostic Index (il~1). We also detected the mutations of P抣~EN gene DNA, mRNA and protein expresstion of Raj i Jurkat cells. We observed the effect of the PTEN protein on CTX (cyclophosphamicle), Ara-C (Cytosine Arabinoside) -induced apoptosis in Raji, Jurkat cells to explore the effects of the turmor suppressor PTEN on CTX, Am-C-induced apoptosis in Raji, .Iurkat cells. Method A total of 60 patients diagnoscd as DLBCL on the basis of histopathology and immunOhistochemistry from 1994 to 1999 admitted to the first I-lospital of the medical Collage, Jinan university were analysed. Most patients treated by the CHOP regimen (cyclophosphamide, doxorubicin, vincristine and prednisone). 45 male (75.0%) and 15 female (25.0%) with a median age of 48 years (range, 8 to 74). 12 patients (4.1 .6%) were above 60 years. The diagnoses of all patients were DLBCL according to the REAL Classiftcatin. According to the Working Formulation (WF), 22 patients presented with diffuse mixed, 31 with diffuse large cell and 7 with immunoblastic lymphoma. Primary nodal presentation was present in 41 cases (68.3%) and primary extranodal presentation in 19 (31.7%). The numbers of extranodal disease in 11 patients were over one site. According to Ann Arbor staging system, 7(11.7%) patients were classified as stage I, 30(50.0%) stage II, 13(21.7%) stage III and 10(16.7%) stage IV. The serum LDI-I levels exceeded 500uIL in 17 patients. Performance status of 19 patients was more than 1 scale based on ECOG criteria.