Higher frequency of p53 gene mutations in diffuse large B‐cell lymphoma with MALT component

Abstract

p53 gene mutation is not a frequent event in the tumorigenesis of lymphomas and the expression of p53 protein is independent of p53 gene mutations. The present study aimed to investigate mutations in the p53 gene in a series of extranodal B-cell lymphomas, and its association with p53 protein expression. A total of 52 cases were graded histologically into Grade 1, Grade 2 and Grade 3 tumors and p53 protein expression was detected using immunohistochemistry. Mutations in the p53 gene were analyzed using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and mobility shifts were confirmed by direct sequencing. The tumors comprised 26 (50%) Grade 1, 9 (17%) Grade 2 and 15 (29%) Grade 3. A high proportion of Grade 2 (25%) tumors expressed p53 protein (P = 0.051) and carried p53 gene mutation (33%) (P = 0.218). However, p53 protein expression was not associated with p53 gene mutations (P = 0.057). Transversion mutations (88%) were more frequently detected than transition mutations (12%). The present study revealed that p53 gene mutations and p53 protein expression occurred in higher frequencies in Grade 2 tumors, which may be of pathogenetic importance. The high frequency of transversion mutations may reflect the influence of an etiological agent in the tumorigenesis of mucosa-associated lymphoid tissue (MALT lymphoma).

Polycomb proteins control proliferation and transformation independently of cell cycle checkpoints by regulating DNA replication

“…Ezh2 enzymatic activity has become an appealing pharmacological target to stop tumour spreading323334, and our data genetically support the effectiveness of PcG inhibition for cancer treatment. For example, it has recently been demonstrated that diffuse large B-cell lymphomas that carry hyperactivating mutations of Ezh2 (whereby diffuse large B-cell lymphomas frequently present defective p53 responses5556), can be efficiently treated with Ezh2-selective compounds33.…”

The significance of TP53 in lymphoid malignancies: mutation prevalence, regulation, prognostic impact and potential as a therapeutic target

“…In lymphomas, the incidence of TP53 mutations and other abnormalities varies significantly according to histological subtype and disease stage. Generally, a low mutation rate is observed in low‐grade non‐Hodgkin lymphoma (NHL), whereas a higher incidence is observed in many aggressive NHL subtypes, especially in those derived from transformation of low‐grade NHL (Lo Coco et al , 1993; Sander et al , 1993; Tai et al , 2004). Studies have consistently demonstrated that TP53 abnormalities, including overexpression, allelic loss, and mutations, have all been associated with poor treatment response and shorter survival (Peller & Rotter, 2003).…”

Missense mutation with/without nonsense mutation of the p53 gene is associated with large cell morphology in human malignant lymphoma

“…A higher incidence of p53 mutation is observed in high-grade NHL, especially in those derived from transformation or progression of lowergrade NHL. [19][20][21] Mutations of the p53 gene are associated with histological transformation of follicular lymphoma 20 and B-cell chronic lymphocytic leukemia, 14 and with the blastic variant of mantle cell lymphoma. 22 As aforementioned, many studies have investigated p53 gene mutations in relation to histopathological type of NHL.…”

“…A low mutation rate is observed in low‐grade NHL. A higher incidence of p53 mutation is observed in high‐grade NHL, especially in those derived from transformation or progression of lower‐grade NHL 19–21 . Mutations of the p53 gene are associated with histological transformation of follicular lymphoma 20 and B‐cell chronic lymphocytic leukemia, 14 and with the blastic variant of mantle cell lymphoma 22 .…”