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TWIST2 Demonstrates Differential Methylation in Immunoglobulin Variable Heavy Chain Mutated and Unmutated Chronic Lymphocytic Leukemia
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| Zeitschriftentitel: | Journal of Clinical Oncology |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , |
| In: | Journal of Clinical Oncology, 23, 2005, 17, S. 3877-3885 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society of Clinical Oncology (ASCO)
|
| Schlagwörter: |
| author_facet |
Raval, Aparna Lucas, David M. Matkovic, Jennifer J. Bennett, Kristi L. Liyanarachchi, Sandya Young, Donn C. Rassenti, Laura Kipps, Thomas J. Grever, Michael R. Byrd, John C. Plass, Christoph Raval, Aparna Lucas, David M. Matkovic, Jennifer J. Bennett, Kristi L. Liyanarachchi, Sandya Young, Donn C. Rassenti, Laura Kipps, Thomas J. Grever, Michael R. Byrd, John C. Plass, Christoph |
|---|---|
| author |
Raval, Aparna Lucas, David M. Matkovic, Jennifer J. Bennett, Kristi L. Liyanarachchi, Sandya Young, Donn C. Rassenti, Laura Kipps, Thomas J. Grever, Michael R. Byrd, John C. Plass, Christoph |
| spellingShingle |
Raval, Aparna Lucas, David M. Matkovic, Jennifer J. Bennett, Kristi L. Liyanarachchi, Sandya Young, Donn C. Rassenti, Laura Kipps, Thomas J. Grever, Michael R. Byrd, John C. Plass, Christoph Journal of Clinical Oncology TWIST2 Demonstrates Differential Methylation in Immunoglobulin Variable Heavy Chain Mutated and Unmutated Chronic Lymphocytic Leukemia Cancer Research Oncology |
| author_sort |
raval, aparna |
| spelling |
Raval, Aparna Lucas, David M. Matkovic, Jennifer J. Bennett, Kristi L. Liyanarachchi, Sandya Young, Donn C. Rassenti, Laura Kipps, Thomas J. Grever, Michael R. Byrd, John C. Plass, Christoph 0732-183X 1527-7755 American Society of Clinical Oncology (ASCO) Cancer Research Oncology http://dx.doi.org/10.1200/jco.2005.02.196 <jats:sec><jats:title>Purpose</jats:title><jats:p> Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease for which natural history can be predicted based on the presence or absence of immunoglobulin (Ig) variable heavy chain (V<jats:sub>H</jats:sub>) gene mutations. Herein we report selective epigenetic silencing of the transcription factor TWIST2 (DERMO1) in Ig V<jats:sub>H</jats:sub> mutated CLL and describe a semiquantitative assay to study promoter methylation of this gene in primary tumor cells. </jats:p></jats:sec><jats:sec><jats:title>Materials and Methods</jats:title><jats:p> TWIST2 promoter methylation was identified by restriction landmark genome scanning. Southern blot (SB), bisulfite sequencing, and combined bisulfite restriction analysis (COBRA), and quantitative SB-COBRA was performed to study methylation of the TWIST2 promoter. Reverse transcription polymerase chain reaction assays were used to study TWIST2 expression in CLL cells. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> Following identification and confirmation of TWIST2 methylation in CLL patients, we demonstrated that expression of this transcription factor is related to the degree of promoter methylation. Expression of TWIST2 in a CLL cell line in which the promoter is methylated was increased following decitabine treatment. We next studied 53 patients by COBRA and demonstrated that 72% of patient samples with mutated Ig V<jats:sub>H</jats:sub> show TWIST2 methylation, while only 16% of patient samples with unmutated Ig V<jats:sub>H</jats:sub> were methylated (P < .001). In a subset of patients, methylation of TWIST2 correlated with mRNA expression. </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> TWIST2 is differentially methylated in CLL cells relative to Ig V<jats:sub>H</jats:sub> mutational status and can be quantitatively monitored by SB-COBRA. Based on the known role of TWIST2 in silencing p53 function in other malignancies, future studies should focus on the role of TWIST2 in CLL and related lymphoproliferative diseases. </jats:p></jats:sec> <i>TWIST2</i> Demonstrates Differential Methylation in Immunoglobulin Variable Heavy Chain Mutated and Unmutated Chronic Lymphocytic Leukemia Journal of Clinical Oncology |
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American Society of Clinical Oncology (ASCO), 2005 |
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American Society of Clinical Oncology (ASCO), 2005 |
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1527-7755 0732-183X |
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American Society of Clinical Oncology (ASCO) |
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Journal of Clinical Oncology |
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| title |
TWIST2 Demonstrates Differential Methylation in Immunoglobulin Variable Heavy Chain Mutated and Unmutated Chronic Lymphocytic Leukemia |
| title_unstemmed |
TWIST2 Demonstrates Differential Methylation in Immunoglobulin Variable Heavy Chain Mutated and Unmutated Chronic Lymphocytic Leukemia |
| title_full |
TWIST2 Demonstrates Differential Methylation in Immunoglobulin Variable Heavy Chain Mutated and Unmutated Chronic Lymphocytic Leukemia |
| title_fullStr |
TWIST2 Demonstrates Differential Methylation in Immunoglobulin Variable Heavy Chain Mutated and Unmutated Chronic Lymphocytic Leukemia |
| title_full_unstemmed |
TWIST2 Demonstrates Differential Methylation in Immunoglobulin Variable Heavy Chain Mutated and Unmutated Chronic Lymphocytic Leukemia |
| title_short |
TWIST2 Demonstrates Differential Methylation in Immunoglobulin Variable Heavy Chain Mutated and Unmutated Chronic Lymphocytic Leukemia |
| title_sort |
<i>twist2</i> demonstrates differential methylation in immunoglobulin variable heavy chain mutated and unmutated chronic lymphocytic leukemia |
| topic |
Cancer Research Oncology |
| url |
http://dx.doi.org/10.1200/jco.2005.02.196 |
| publishDate |
2005 |
| physical |
3877-3885 |
| description |
<jats:sec><jats:title>Purpose</jats:title><jats:p> Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease for which natural history can be predicted based on the presence or absence of immunoglobulin (Ig) variable heavy chain (V<jats:sub>H</jats:sub>) gene mutations. Herein we report selective epigenetic silencing of the transcription factor TWIST2 (DERMO1) in Ig V<jats:sub>H</jats:sub> mutated CLL and describe a semiquantitative assay to study promoter methylation of this gene in primary tumor cells. </jats:p></jats:sec><jats:sec><jats:title>Materials and Methods</jats:title><jats:p> TWIST2 promoter methylation was identified by restriction landmark genome scanning. Southern blot (SB), bisulfite sequencing, and combined bisulfite restriction analysis (COBRA), and quantitative SB-COBRA was performed to study methylation of the TWIST2 promoter. Reverse transcription polymerase chain reaction assays were used to study TWIST2 expression in CLL cells. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> Following identification and confirmation of TWIST2 methylation in CLL patients, we demonstrated that expression of this transcription factor is related to the degree of promoter methylation. Expression of TWIST2 in a CLL cell line in which the promoter is methylated was increased following decitabine treatment. We next studied 53 patients by COBRA and demonstrated that 72% of patient samples with mutated Ig V<jats:sub>H</jats:sub> show TWIST2 methylation, while only 16% of patient samples with unmutated Ig V<jats:sub>H</jats:sub> were methylated (P < .001). In a subset of patients, methylation of TWIST2 correlated with mRNA expression. </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> TWIST2 is differentially methylated in CLL cells relative to Ig V<jats:sub>H</jats:sub> mutational status and can be quantitatively monitored by SB-COBRA. Based on the known role of TWIST2 in silencing p53 function in other malignancies, future studies should focus on the role of TWIST2 in CLL and related lymphoproliferative diseases. </jats:p></jats:sec> |
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| author | Raval, Aparna, Lucas, David M., Matkovic, Jennifer J., Bennett, Kristi L., Liyanarachchi, Sandya, Young, Donn C., Rassenti, Laura, Kipps, Thomas J., Grever, Michael R., Byrd, John C., Plass, Christoph |
| author_facet | Raval, Aparna, Lucas, David M., Matkovic, Jennifer J., Bennett, Kristi L., Liyanarachchi, Sandya, Young, Donn C., Rassenti, Laura, Kipps, Thomas J., Grever, Michael R., Byrd, John C., Plass, Christoph, Raval, Aparna, Lucas, David M., Matkovic, Jennifer J., Bennett, Kristi L., Liyanarachchi, Sandya, Young, Donn C., Rassenti, Laura, Kipps, Thomas J., Grever, Michael R., Byrd, John C., Plass, Christoph |
| author_sort | raval, aparna |
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| description | <jats:sec><jats:title>Purpose</jats:title><jats:p> Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease for which natural history can be predicted based on the presence or absence of immunoglobulin (Ig) variable heavy chain (V<jats:sub>H</jats:sub>) gene mutations. Herein we report selective epigenetic silencing of the transcription factor TWIST2 (DERMO1) in Ig V<jats:sub>H</jats:sub> mutated CLL and describe a semiquantitative assay to study promoter methylation of this gene in primary tumor cells. </jats:p></jats:sec><jats:sec><jats:title>Materials and Methods</jats:title><jats:p> TWIST2 promoter methylation was identified by restriction landmark genome scanning. Southern blot (SB), bisulfite sequencing, and combined bisulfite restriction analysis (COBRA), and quantitative SB-COBRA was performed to study methylation of the TWIST2 promoter. Reverse transcription polymerase chain reaction assays were used to study TWIST2 expression in CLL cells. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> Following identification and confirmation of TWIST2 methylation in CLL patients, we demonstrated that expression of this transcription factor is related to the degree of promoter methylation. Expression of TWIST2 in a CLL cell line in which the promoter is methylated was increased following decitabine treatment. We next studied 53 patients by COBRA and demonstrated that 72% of patient samples with mutated Ig V<jats:sub>H</jats:sub> show TWIST2 methylation, while only 16% of patient samples with unmutated Ig V<jats:sub>H</jats:sub> were methylated (P < .001). In a subset of patients, methylation of TWIST2 correlated with mRNA expression. </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> TWIST2 is differentially methylated in CLL cells relative to Ig V<jats:sub>H</jats:sub> mutational status and can be quantitatively monitored by SB-COBRA. Based on the known role of TWIST2 in silencing p53 function in other malignancies, future studies should focus on the role of TWIST2 in CLL and related lymphoproliferative diseases. </jats:p></jats:sec> |
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| imprint_str_mv | American Society of Clinical Oncology (ASCO), 2005 |
| institution | DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161 |
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| spelling | Raval, Aparna Lucas, David M. Matkovic, Jennifer J. Bennett, Kristi L. Liyanarachchi, Sandya Young, Donn C. Rassenti, Laura Kipps, Thomas J. Grever, Michael R. Byrd, John C. Plass, Christoph 0732-183X 1527-7755 American Society of Clinical Oncology (ASCO) Cancer Research Oncology http://dx.doi.org/10.1200/jco.2005.02.196 <jats:sec><jats:title>Purpose</jats:title><jats:p> Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease for which natural history can be predicted based on the presence or absence of immunoglobulin (Ig) variable heavy chain (V<jats:sub>H</jats:sub>) gene mutations. Herein we report selective epigenetic silencing of the transcription factor TWIST2 (DERMO1) in Ig V<jats:sub>H</jats:sub> mutated CLL and describe a semiquantitative assay to study promoter methylation of this gene in primary tumor cells. </jats:p></jats:sec><jats:sec><jats:title>Materials and Methods</jats:title><jats:p> TWIST2 promoter methylation was identified by restriction landmark genome scanning. Southern blot (SB), bisulfite sequencing, and combined bisulfite restriction analysis (COBRA), and quantitative SB-COBRA was performed to study methylation of the TWIST2 promoter. Reverse transcription polymerase chain reaction assays were used to study TWIST2 expression in CLL cells. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> Following identification and confirmation of TWIST2 methylation in CLL patients, we demonstrated that expression of this transcription factor is related to the degree of promoter methylation. Expression of TWIST2 in a CLL cell line in which the promoter is methylated was increased following decitabine treatment. We next studied 53 patients by COBRA and demonstrated that 72% of patient samples with mutated Ig V<jats:sub>H</jats:sub> show TWIST2 methylation, while only 16% of patient samples with unmutated Ig V<jats:sub>H</jats:sub> were methylated (P < .001). In a subset of patients, methylation of TWIST2 correlated with mRNA expression. </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> TWIST2 is differentially methylated in CLL cells relative to Ig V<jats:sub>H</jats:sub> mutational status and can be quantitatively monitored by SB-COBRA. Based on the known role of TWIST2 in silencing p53 function in other malignancies, future studies should focus on the role of TWIST2 in CLL and related lymphoproliferative diseases. </jats:p></jats:sec> <i>TWIST2</i> Demonstrates Differential Methylation in Immunoglobulin Variable Heavy Chain Mutated and Unmutated Chronic Lymphocytic Leukemia Journal of Clinical Oncology |
| spellingShingle | Raval, Aparna, Lucas, David M., Matkovic, Jennifer J., Bennett, Kristi L., Liyanarachchi, Sandya, Young, Donn C., Rassenti, Laura, Kipps, Thomas J., Grever, Michael R., Byrd, John C., Plass, Christoph, Journal of Clinical Oncology, TWIST2 Demonstrates Differential Methylation in Immunoglobulin Variable Heavy Chain Mutated and Unmutated Chronic Lymphocytic Leukemia, Cancer Research, Oncology |
| title | TWIST2 Demonstrates Differential Methylation in Immunoglobulin Variable Heavy Chain Mutated and Unmutated Chronic Lymphocytic Leukemia |
| title_full | TWIST2 Demonstrates Differential Methylation in Immunoglobulin Variable Heavy Chain Mutated and Unmutated Chronic Lymphocytic Leukemia |
| title_fullStr | TWIST2 Demonstrates Differential Methylation in Immunoglobulin Variable Heavy Chain Mutated and Unmutated Chronic Lymphocytic Leukemia |
| title_full_unstemmed | TWIST2 Demonstrates Differential Methylation in Immunoglobulin Variable Heavy Chain Mutated and Unmutated Chronic Lymphocytic Leukemia |
| title_short | TWIST2 Demonstrates Differential Methylation in Immunoglobulin Variable Heavy Chain Mutated and Unmutated Chronic Lymphocytic Leukemia |
| title_sort | <i>twist2</i> demonstrates differential methylation in immunoglobulin variable heavy chain mutated and unmutated chronic lymphocytic leukemia |
| title_unstemmed | TWIST2 Demonstrates Differential Methylation in Immunoglobulin Variable Heavy Chain Mutated and Unmutated Chronic Lymphocytic Leukemia |
| topic | Cancer Research, Oncology |
| url | http://dx.doi.org/10.1200/jco.2005.02.196 |