Proteomic-Based Profiling of Lymphomas: Chromatin Proteomics; Composition and Modification of Histone and Non-Histone Chromosomal Proteins

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT01563874
First received: March 23, 2012
Last updated: August 22, 2014
Last verified: August 2014
  Purpose

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.

...


Condition
Lymphoma
Leukemia
Lymphoid Hyperplasia

Study Type: Observational
Study Design: Time Perspective: Retrospective
Official Title: Proteomic-Based Profiling of Lymphomas: Chromatin Proteomics; Composition and Modification of Histone and Non-Histone Chromosomal Proteins

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Enrollment: 130
Study Start Date: May 2009
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • 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 superceding 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 superceding protocols. Samples from minors < 18 years old will not be used.

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01563874

Locations
United States, Maryland
National Cancer Institute (NCI), 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: David L Levens, M.D. National Cancer Institute (NCI)
  More Information

No publications provided

Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT01563874     History of Changes
Obsolete Identifiers: NCT00952809
Other Study ID Numbers: 999909155, 09-C-N155
Study First Received: March 23, 2012
Last Updated: August 22, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Antibodies
Reverse Phase Microarrays
Epigenetics
Acetylation
Methylation
Lymphoma

Additional relevant MeSH terms:
Hyperplasia
Lymphoma
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on October 19, 2014