Different incidence and pattern of p15INK4b and p16INK4a promoter region hypermethylation in Hodgkin's and CD30-Positive non-Hodgkin's lymphomas.
The p16INK4a and p15INK4b 5' CpG island hypermethylation has been described as one of the most frequent mechanisms leading to inactivation of these tumor suppressor genes in hematological malignancies. The p16 and p15 promoter regions were studied using methylation-specific polymerase chain reaction in 53 CD30 non-Hodgkin's lymphomas (25 anaplastic large-cell, 13 peripheral T cell, and 15 anaplastic diffuse large B cell) and 26 Hodgkin's lymphomas, with the aim of comparing the methylation status of these tumor suppressor genes in anaplastic large-cell lymphomas and other related entities. p16 and p15 methylation was detected, respectively, in 28% and 60% of CD30 non-Hodgkin's lymphomas and in 38% and 42% of Hodgkin's neoplasms. This confirms the p16-methylated status in Hodgkin's cases described in a single previous study and adds information concerning the p15 gene that was also found to be methylated in this lymphoma subtype. Methylation incidence within cases at diagnosis and at relapse suggests that it is an early event in anaplastic large-cell lymphomas, being involved in tumor progression in Hodgkin's cases. Our results show that although p16 and/or p15 methylation is involved in non-Hodgkin's and Hodgkin's tumors that share morphological and phenotypic features, differences in incidence, pattern of methylation, and implication in tumor progression are observed.
García
María J
MJ
Department of Pathology, Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain.
Martínez-Delgado
Beatriz
B
Cebrian
Arancha
A
Martínez
Angel
A
Benítez
Javier
J
Rivas
Carmen
C
D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D006689:Hodgkin Disease / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017730:Ki-1 Antigen; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D012008:Recurrence; D025521:Tumor Suppressor Proteins
C493966:CDKN2B protein, human; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D017730:Ki-1 Antigen; D025521:Tumor Suppressor Proteins