| Autor: |
Villuendas, Raquel, Sánchez-Beato, Margarita, Martínez, Juan C., Saez, Ana I., Martinez-Delgado, Beatriz, García, Juan F., Mateo, M. Sol, Sanchez-Verde, L., Benítez, Javier, Martínez, Pedro, Piris, Miguel A. |
| Zdroj: |
American Journal of Pathology; September 1998, Vol. 153 Issue: 3 p887-897, 11p |
| Abstrakt: |
The CDKN2Agene located on chromosome region 9p21 encodes the cyclin-dependent kinase-4 inhibitor p16/INK4A, a negative cell cycle regulator. We analyzed p16/INK4A expression in different types of non-Hodgkin's lymphoma to determine whether the absence of this protein is involved in lymphomagenesis, while also trying to characterize the genetic events underlying this p16/INK4A loss. To this end, we investigated the levels of p16/INK4A protein using immunohistochemical techniques in 153 cases of non-Hodgkin's lymphoma, using as reference the levels found in reactive lymphoid tissue. The existence of gene mutation, CpG island methylation, and allelic loss were investigated in a subset of 26 cases, using single-strand conformational polymorphism and direct sequencing, Southern Blot, polymerase chain reaction, and microsatellite analysis, respectively. Loss of p16/INK4A expression was detected in 41 of the 112 non-Hodgkin's lymphomas studied (37%), all of which corresponded to high-grade tumors. This loss of p16/INK4A was found more frequently in cases showing tumor progression from mucosa-associated lymphoid tissue low-grade lymphomas (31 of 37) or follicular lymphomas (4 of 4) into diffuse large B-cell lymphomas. Analysis of the status of the p16/INK4Agene showed different genetic alterations (methylation of the 5′-CpG island of thep16/INK4Agene, 6 of 23 cases; allelic loss at 9p21, 3 of 16 cases; and nonsense mutation, 1 of 26 cases). In all cases, these events were associated with loss of the p16/INK4A protein. No case that preserved protein expression contained any genetic change. Our results demonstrate that p16/INK4A loss of expression contributes to tumor progression in lymphomas. The most frequent genetic alterations found were 5′-CpG island methylation and allelic loss. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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