DNA Methylation Profiles of Lymphoid and Hematopoietic Malignancies

Takao Takahashi, Narayan Shivapurkar, Jyotsna Reddy, Hisayuki Shigematsu, Kuniharu Miyajima, Makoto Suzuki, Shinichi Toyooka, Sabine Zöchbauer-Müller, Johannes Drach, Gunjan Parikh, Yingye Zheng, Ziding Feng, Steven H. Kroft, Charles Timmons, Robert W. McKenna, Adi F. Gazdar

Research output: Contribution to journalArticle

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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 (b) 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 "hall-marks 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.

Original languageEnglish (US)
Pages (from-to)2928-2935
Number of pages8
JournalClinical Cancer Research
Volume10
Issue number9
DOIs
StatePublished - May 1 2004

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Hematologic Neoplasms
DNA Methylation
Methylation
Monoclonal Gammopathy of Undetermined Significance
Multiple Myeloma
Genes
Neoplasms
Tumor Suppressor Genes
Lymphoma
Leukemia
Paraproteinemias
Genetic Promoter Regions
Gene Frequency
Epigenomics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Takahashi, T., Shivapurkar, N., Reddy, J., Shigematsu, H., Miyajima, K., Suzuki, M., ... Gazdar, A. F. (2004). DNA Methylation Profiles of Lymphoid and Hematopoietic Malignancies. Clinical Cancer Research, 10(9), 2928-2935. https://doi.org/10.1158/1078-0432.CCR-03-0716

DNA Methylation Profiles of Lymphoid and Hematopoietic Malignancies. / Takahashi, Takao; Shivapurkar, Narayan; Reddy, Jyotsna; Shigematsu, Hisayuki; Miyajima, Kuniharu; Suzuki, Makoto; Toyooka, Shinichi; Zöchbauer-Müller, Sabine; Drach, Johannes; Parikh, Gunjan; Zheng, Yingye; Feng, Ziding; Kroft, Steven H.; Timmons, Charles; McKenna, Robert W.; Gazdar, Adi F.

In: Clinical Cancer Research, Vol. 10, No. 9, 01.05.2004, p. 2928-2935.

Research output: Contribution to journalArticle

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 2004, 'DNA Methylation Profiles of Lymphoid and Hematopoietic Malignancies', Clinical Cancer Research, vol. 10, no. 9, pp. 2928-2935. https://doi.org/10.1158/1078-0432.CCR-03-0716
Takahashi T, Shivapurkar N, Reddy J, Shigematsu H, Miyajima K, Suzuki M et al. DNA Methylation Profiles of Lymphoid and Hematopoietic Malignancies. Clinical Cancer Research. 2004 May 1;10(9):2928-2935. https://doi.org/10.1158/1078-0432.CCR-03-0716
Takahashi, Takao ; Shivapurkar, Narayan ; Reddy, Jyotsna ; Shigematsu, Hisayuki ; Miyajima, Kuniharu ; Suzuki, Makoto ; Toyooka, Shinichi ; Zöchbauer-Müller, Sabine ; Drach, Johannes ; Parikh, Gunjan ; Zheng, Yingye ; Feng, Ziding ; Kroft, Steven H. ; Timmons, Charles ; McKenna, Robert W. ; Gazdar, Adi F. / DNA Methylation Profiles of Lymphoid and Hematopoietic Malignancies. In: Clinical Cancer Research. 2004 ; Vol. 10, No. 9. pp. 2928-2935.
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AU - Takahashi, Takao

AU - Shivapurkar, Narayan

AU - Reddy, Jyotsna

AU - Shigematsu, Hisayuki

AU - Miyajima, Kuniharu

AU - Suzuki, Makoto

AU - Toyooka, Shinichi

AU - Zöchbauer-Müller, Sabine

AU - Drach, Johannes

AU - Parikh, Gunjan

AU - Zheng, Yingye

AU - Feng, Ziding

AU - Kroft, Steven H.

AU - Timmons, Charles

AU - McKenna, Robert W.

AU - Gazdar, Adi F.

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N2 - 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 (b) 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 "hall-marks 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.

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