Faculty Collaboration Database

DNA methylation profiles of lymphoid and hematopoietic malignancies. Clin Cancer Res 2004 May 01;10(9):2928-35

Date

05/08/2004

Pubmed ID

15131027

DOI

10.1158/1078-0432.ccr-03-0716

Scopus ID

2-s2.0-2442628250 (requires institutional sign-in at Scopus site)   53 Citations

Abstract

PURPOSE: Aberrant methylation of the 5' gene promoter regions is an epigenetic phenomenon that is the major mechanism for silencing of tumor suppressor genes in many cancer types. The aims of our study were (a) to compare the methylation profiles of the major forms of hematological malignancies and (b) to determine the methylation profile of monoclonal gammopathy of undetermined significance (MGUS) and compare it with that of multiple myeloma (MM).

EXPERIMENTAL DESIGN: We compared the aberrant promoter methylation profile of 14 known or suspected tumor suppressor genes in leukemias (n = 48), lymphomas (n = 42), and MMs (n = 40). We also examined the methylation profile of MGUS (n = 20), a premalignant plasma cell dyscrasia. The genes studied represent five of the six "hallmarks of cancer."

RESULTS: Peripheral blood lymphocytes (n = 14) from healthy volunteers were negative for methylation of all genes, and methylation percentages in 41 nonmalignant tissues (peripheral blood mononuclear cells, bone marrows, and lymph nodes) from hematological patients were low (0-9%) for all 14 genes, confirming that methylation was tumor specific. Ten of the genes were methylated at frequencies of 29-68% in one or more tumor types, and the methylation indices (an indicator of overall methylation) varied from 0.25 to 0.34. With two exceptions, the methylation patterns of leukemias and lymphomas were similar. However, the pattern of MMs varied from the other tumor types for six genes. In general, the methylation pattern of MGUS was similar to that of MM, although the methylation frequencies were lower (the methylation index of MGUS was 0.15, and that of MM was 0.3). However, the methylation frequencies of six genes were significantly higher in MGUS than in control tissues. The relatively high frequencies of methylation in MGUS are consistent with it being a premalignant condition.

CONCLUSIONS: The three major forms of lymphoid/hematopoietic malignancies show overlapping but individual patterns of methylation.

Author List

Takahashi T, Shivapurkar N, Reddy J, Shigematsu H, Miyajima K, Suzuki M, Toyooka S, Zöchbauer-Müller S, Drach J, Parikh G, Zheng Y, Feng Z, Kroft SH, Timmons C, McKenna RW, Gazdar AF

Author

Steven Howard Kroft MD Chair, Professor in the Pathology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Age Factors
Antimetabolites, Antineoplastic
Azacitidine
Cell Line, Tumor
DNA Methylation
DNA, Neoplasm
Female
Gene Expression Regulation, Neoplastic
Genes, Tumor Suppressor
Humans
Leukemia
Logistic Models
Lymphoma
Male
Middle Aged
Multiple Myeloma
Promoter Regions, Genetic
Sex Factors