Significance of CDKN2A gene A148T variant in patients with bladder cancer

Abstract

ObjectivesThe A148T polymorphism of CDKN2A gene is observed in various neoplasms with the incidence rate of 3-35%, however, rather little is known either about the frequency of its occurrence or of its significance in urinary bladder carcinoma.Materials and methodsDNA was isolated from blood of 156 patients with urinary bladder carcinoma (130 men). In histopathology, 84 cases were classified as G1, 42 as G2, and 30 as G3. The clinical stage was in 81 cases estimated at Ta and in 75 cases at T1-T4. A148T polymorphism was detected by the MSSCP technique and by sequencing.ResultsA148T polymorphism was identified in 9/156 urinary bladder carcinoma cases (only in men). The obtained results were compared with the polymorphism incidence for the Polish population, estimated by Debniak et al. The occurrence in the group of the bladder cancer patients turned out higher (5.77%) from that in the control group (2.89%) (G test, table 2×2: NBLADDER CANCER = 156, NCONTROL = 1210, G = 4.298, p <0.05).ConclusionSumming up and taking into account the analysis of clinical parameters and the age of the disease occurrence, the A148T polymorphism of CDKN2A gene was identified in the study group only in men, in whom the disease was diagnosed above the age of 60, while the diagnosed neoplasms were in the majority of cases characterized by higher clinical stages and higher grades of malignancy. This has been the first study that attempted to show a potential association between A148T alterations and an increased risk for bladder cancer development.

Integrative genomic analysis focused on cell cycle genes for MYC-driven aggressive mature B-cell lymphoma

“…The other frequent molecular alterations in Category I are alterations of CDKN2A that encode two cycle-dependent kinase inhibitors, p16INK4a and p14AR, which directly negatively regulate the cell cycle like p53. 39 Deletion of this gene is a prognostic factor in many tumors 40 and missense mutations of this gene were detected previously in some DLBCL cases. 41 The common CDKN2A polymorphism p.A148T found in 4 cases was previously described in several cancer types such as colon-, lung-, breast-, bladder-cancer and melanoma.…”

“…41 The common CDKN2A polymorphism p.A148T found in 4 cases was previously described in several cancer types such as colon-, lung-, breast-, bladder-cancer and melanoma. 40 , 42 This variant and amino acid change located in exon 2 of CDKN2A and in the open reading frame of p16INK4a are not directly involved in binding to cyclin kinases, CDK4 or CDK6. Thus, this variant (p.A148T) may not have direct effects on the inhibitor activity, but the functional impact is unclear.…”

Molecular subtyping of bladder cancer using Kohonen self‐organizing maps

“…Mutations in TP53 (exons 4–8), CDKN2A (Cyclin‐Dependent Kinase inhibitor 2A , exons 1 α , 2, and 3), and FGFR3 (exons 7, 10, 15) were detected using single strand conformational polymorphism (SSCP) analysis and Sanger sequencing, as detailed . The mutations in CHEK2 (Chekpoint Kinase, IVS2 + 1G>A, 1100delC, and I157T) gene were detected using multiplex PCR .…”