Τίτλος:
Mutational and methylation analysis of the cyclin-dependent kinase 4
inhibitor (p16(INK4A)) gene in chronic lymphocytic leukemia
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Objectives: Chronic lymphocytic leukemia (CLL) comprises a heterogenous
group of at least two types of disease entities characterized by
distinctive clinical, immunophenotypical and genetic features. The
molecular mechanisms underlying the pathogenesis and the histological
transformation of CLL are not well known. The INK4A/p16, a cyclin
dependent kinase inhibitor has been considered as a tumor suppressor
gene. Inactivation of this gene by homozygous deletions, mutations and
hypermethylation occurs in a variety of human neoplasms. The aim of the
present study was to determine the frequency of p16 gene deletions and
mutations as well as the methylation status of the same gene in CLL
patients. Methods: We examined 34 samples from CLL patients by Southern
Blotting, Single-Strand Conformation Polymorphism (SSCP), DNA sequencing
and Methylation-Specific PCR. Results: Southern Blot analysis revealed
non-rearranged bands in 33/34 cases. Homozygous deletions were not
observed in any case. In 1/34 case a rearranged band was detected with
EcoRI enzyme. The PCR-SSCP analysis of exons 1 and 3 revealed normal
pattern of migration in all cases examined. The analysis of exon 2
revealed abnormal migration pattern in 2/34 cases (5.8%). Sequencing of
these cases revealed the presence of the ALA148THR polymorphism.
Methylation analysis of p16 gene promoter revealed hypermethylation of
CpG islands in 6/34 cases (17.6%). Conclusion: These results indicate
that genetic alterations of p16 gene are rare events in patients with
CLL. The clarification of the role of p16 gene promoter methylation in
the pathogenesis and evolution of CLL needs further investigation.
Συγγραφείς:
Tsirigotis, P
Pappa, V
Labropoulos, S
Papageorgiou, S and
Kontsioti, F
Dervenoulas, J
Papageorgiou, E
Panani, A and
Mantzios, G
Economopoulos, T
Raptis, S
Περιοδικό:
European Journal of Haematology
Λέξεις-κλειδιά:
chronic lymphocytic leukemia; p16/INK4A gene; mutation; deletion;
promoter methylation; methylation specific polymerase chain reaction
DOI:
10.1111/j.1600-0609.2005.00604.x
