Proteomic-Based Profiling of Lymphomas: Chromatin Proteomics; Composition and Modification of Histone and Non-Histone Chromosomal Proteins
| Status: | Completed |
|---|---|
| Conditions: | Lymphoma, Hematology |
| Therapuetic Areas: | Hematology, Oncology |
| Healthy: | No |
| Age Range: | 18 - 100 |
| Updated: | 9/26/2018 |
| Start Date: | June 2, 2009 |
BACKGROUND:
Lymphomas are comprised of a diversity of tumors with different pathologic and clinical
features. While distinct differences in gene expression profiles have been elucidated in
different lymphomas, there has been inconsistent correlation with the few published proteomic
studies.
Greater insights into the biology of lymphomas may be achieved by integrating current genomic
information with additional studies focused on the interrelationships in tumors of the
patterns of chromatin protein expression, chromatin protein modification, and RNA expression
profiling (both within bulk tumor and within specific microscopic tumor niches accessible by
microdissection and cell sorting approaches).
OBJECTIVES:
The goals of this protocol are to identify the global levels of all histones (including
variant histones) and non-histone chromosomal proteins, and to measure the relative levels of
most known covalent modifications on histone and non-histone chromosomal proteins.
For a limited number of cases illustrative of selected pathological entities, we propose to
map the genome-wide distribution of those modifications judged to be biochemically
instructive.
ELIGIBILITY:
This work will involve the analysis of a broad panel of lymphoma and lymphoid samples, which
were previously procured under multiple protocols at the NIH, and for which there is excess
tissue available for research. We also request permission to extend this analysis to surplus
materials to be accrued under existing protocols, upon completion of all superseding
diagnostic tests and medical/scientific studies. The criteria for inclusion in this study are
subsumed under the enveloping protocols. The number of cases to be included is dependent upon
the size of these protocols; because statistical significance improves with increasing
numbers. We hope to include up to 300 cases.
DESIGN:
Lysates from surplus samples will be prepared and arrayed onto microarrays.
These arrays will be probed with panels of protein and modification specific antibodies.
The antibody reactivity will be quantified and samples will be subjected to statistical
analysis, especially hierarchical clustering to correlate patterns of reactivity with
clinical and histological features.
Representative cases for which sufficient surplus tissue remains will be subjected to
ChIP-Seq to map the distribution of modifications across the genome.
Lymphomas are comprised of a diversity of tumors with different pathologic and clinical
features. While distinct differences in gene expression profiles have been elucidated in
different lymphomas, there has been inconsistent correlation with the few published proteomic
studies.
Greater insights into the biology of lymphomas may be achieved by integrating current genomic
information with additional studies focused on the interrelationships in tumors of the
patterns of chromatin protein expression, chromatin protein modification, and RNA expression
profiling (both within bulk tumor and within specific microscopic tumor niches accessible by
microdissection and cell sorting approaches).
OBJECTIVES:
The goals of this protocol are to identify the global levels of all histones (including
variant histones) and non-histone chromosomal proteins, and to measure the relative levels of
most known covalent modifications on histone and non-histone chromosomal proteins.
For a limited number of cases illustrative of selected pathological entities, we propose to
map the genome-wide distribution of those modifications judged to be biochemically
instructive.
ELIGIBILITY:
This work will involve the analysis of a broad panel of lymphoma and lymphoid samples, which
were previously procured under multiple protocols at the NIH, and for which there is excess
tissue available for research. We also request permission to extend this analysis to surplus
materials to be accrued under existing protocols, upon completion of all superseding
diagnostic tests and medical/scientific studies. The criteria for inclusion in this study are
subsumed under the enveloping protocols. The number of cases to be included is dependent upon
the size of these protocols; because statistical significance improves with increasing
numbers. We hope to include up to 300 cases.
DESIGN:
Lysates from surplus samples will be prepared and arrayed onto microarrays.
These arrays will be probed with panels of protein and modification specific antibodies.
The antibody reactivity will be quantified and samples will be subjected to statistical
analysis, especially hierarchical clustering to correlate patterns of reactivity with
clinical and histological features.
Representative cases for which sufficient surplus tissue remains will be subjected to
ChIP-Seq to map the distribution of modifications across the genome.
BACKGROUND:
Lymphomas are comprised of a diversity of tumors with different pathologic and clinical
features. While distinct differences in gene expression profiles have been elucidated in
different lymphomas, there has been inconsistent correlation with the few published proteomic
studies.
Greater insights into the biology of lymphomas may be achieved by integrating current genomic
information with additional studies focused on the interrelationships in tumors of the
patterns of chromatin protein expression, chromatin protein modification, and RNA expression
profiling (both within bulk tumor and within specific microscopic tumor niches accessible by
microdissection and cell sorting approaches).
OBJECTIVES:
The goals of this protocol are to identify the global levels of all histones (including
variant histones) and non-histone chromosomal proteins, and to measure the relative levels of
most known covalent modifications on histone and non-histone chromosomal proteins.
For a limited number of cases illustrative of selected pathological entities, we propose to
map the genome-wide distribution of those modifications judged to be biochemically
instructive.
ELIGIBILITY:
This work will involve the analysis of a broad panel of lymphoma and lymphoid samples, which
were previously procured under multiple protocols at the NIH, and for which there is excess
tissue available for research. We also request permission to extend this analysis to surplus
materials to be accrued under existing protocols, upon completion of all superseding
diagnostic tests and medical/scientific studies. The criteria for inclusion in this study are
subsumed under the enveloping protocols. The number of cases to be included is dependent upon
the size of these protocols; because statistical significance improves with increasing
numbers. We hope to include up to 300 cases.
DESIGN:
Lysates from surplus samples will be prepared and arrayed onto microarrays.
These arrays will be probed with panels of protein and modification specific antibodies.
The antibody reactivity will be quantified and samples will be subjected to statistical
analysis, especially hierarchical clustering to correlate patterns of reactivity with
clinical and histological features.
Representative cases for which sufficient surplus tissue remains will be subjected to
ChIP-Seq to map the distribution of modifications across the genome.
Lymphomas are comprised of a diversity of tumors with different pathologic and clinical
features. While distinct differences in gene expression profiles have been elucidated in
different lymphomas, there has been inconsistent correlation with the few published proteomic
studies.
Greater insights into the biology of lymphomas may be achieved by integrating current genomic
information with additional studies focused on the interrelationships in tumors of the
patterns of chromatin protein expression, chromatin protein modification, and RNA expression
profiling (both within bulk tumor and within specific microscopic tumor niches accessible by
microdissection and cell sorting approaches).
OBJECTIVES:
The goals of this protocol are to identify the global levels of all histones (including
variant histones) and non-histone chromosomal proteins, and to measure the relative levels of
most known covalent modifications on histone and non-histone chromosomal proteins.
For a limited number of cases illustrative of selected pathological entities, we propose to
map the genome-wide distribution of those modifications judged to be biochemically
instructive.
ELIGIBILITY:
This work will involve the analysis of a broad panel of lymphoma and lymphoid samples, which
were previously procured under multiple protocols at the NIH, and for which there is excess
tissue available for research. We also request permission to extend this analysis to surplus
materials to be accrued under existing protocols, upon completion of all superseding
diagnostic tests and medical/scientific studies. The criteria for inclusion in this study are
subsumed under the enveloping protocols. The number of cases to be included is dependent upon
the size of these protocols; because statistical significance improves with increasing
numbers. We hope to include up to 300 cases.
DESIGN:
Lysates from surplus samples will be prepared and arrayed onto microarrays.
These arrays will be probed with panels of protein and modification specific antibodies.
The antibody reactivity will be quantified and samples will be subjected to statistical
analysis, especially hierarchical clustering to correlate patterns of reactivity with
clinical and histological features.
Representative cases for which sufficient surplus tissue remains will be subjected to
ChIP-Seq to map the distribution of modifications across the genome.
- INCLUSION CRITERIA:
We propose to analyze the histone and chromatin modifications from several classes of
patients: 1) patients bearing the diagnosis of lymphoid malignancies made or confirmed at
the NIH. Solid tumors of the lymphoid system would constitute the major source of these
tissues, however tissue samples from patients with malignant diagnoses that involve
circulating malignant cells (Mycosis fungoides, Sezary syndrome, etc.) would also be
appropriate for analysis; 2) non-malignant lymphoid tissue obtained for diagnostic purposes
or normal lymphoid tissue obtained incidentally during surgery (in all cases only residual
and surplus tissue will be used, only with the express approval of the appropriate clinical
investigator(s). Primarily included among these tissues would be hyperplastic lymphoid
tissue especially tonsils. Other hyperplastic and non-malignant lymph node samples showing
proliferative responses or sinus histiocytosis would also be appropriate to compare with
the malignant samples.
EXCLUSION CRITERIA:
Only cases with sufficient frozen biopsy material from initial biopsy and/or biopsies at
relapse of disease to obtain adequate tissues lysates for proteomic-based analyses and in
selected cases for ChIPSeq following analysis of RNA expression as performed under
superseding protocols. In some cases, for some histone modifications, it may be possible to
recover appropriate tissue from paraffin embedded blocks, however no such samples will be
used for this study without prior consultation and approval from the clinical investigator
and hematopathologist associated with the superseding protocols. Samples from minors <18
years old will not be used.
We found this trial at
1
site
9609 Medical Center Drive
Bethesda, Maryland 20892
Bethesda, Maryland 20892
1-800-422-6237
National Cancer Institute , 9000 Rockville Pike The National Cancer Institute (NCI) is part of...
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