1. We will perform an exploratory study using whole exome sequencing (WES) on SS MALT lymphoma samples to pick up specific gene mutations enriched or exclusively present in salivary MALT lymphoma in SS patients.2 .We will investigate the relation…
ID
Source
Brief title
Condition
- Lymphomas non-Hodgkin's B-cell
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Detection of recurrent mutations in MALT lymphoma associated with Sjogrens
disease.
Secondary outcome
n.a.
Background summary
Sjögren*s syndrome is an autoimmune disease characterized by dry mouth and
eyes. Patients have a 5% risk of developing a B-cell lymphoma in the salivary
gland. It is largely unknown which genetic changes result in the development of
these lymphomas. By using novel techniques (next generation sequencing) we will
try to establish the basis for the development of these lymphomas.
The UMCG is an expertise center for Sjögren*s syndrome (SS) and ± 40 new
patients are seen annually. SS is a chronic multisystem autoimmune disease
characterized by diminished lacrimal and salivary gland function associated
with lymphocytic infiltration of the secretory glands. In patients with SS
salivary gland enlargement can vary over time, but persistent enlargement
should raise the suspicion of a B-cell lymphoma (B-NHL) which develops in 4-7%
of patients. The marginal zone B-cell lymphoma (MZL) of mucosa associated
lymphoid tissue (MALT lymphoma) constitutes 48%-75% of B-cell lymphoma (B-NHL)
in SS.
The development of SS MALT lymphoma follows after an initial period of
polyclonal B-cell proliferation in the exocrine tissue. Sustained (auto)
antigen stimulation and inflammation can induce oncogenic events, e.g. through
reactive oxygen species, resulting in genetic instability of B-cells. Over
time, multiple disturbances in B-cell differentiation and trafficking result in
oligo-monoclonal B-cell expansion. A current research project at the Department
of Rheumatology and Clinical Immunology sponsored by the Dutch Arthritis
Foundation tests the hypothesis that the MALT lymphoma develop from a
relatively small subset of intraepithelial B-lymphocytes (1)
Relatively little is known about the genetic aberrations that underlie the
development of SS MALT lymphoma. In non-SS MALT lymphoma several chromosomal
translocations can occur. The frequency of translocations t(11;18), t(1;14),
t(14;18) and t(3;14) vary depending on the anatomical localization. These
translocations have in common that they result in constitutive activation of
the nuclear factor-kappa-B (NF-kB) pathway. In SS MALT lymphoma only trisomies
3, 12 and 18 can be found at low frequency (2). The majority of SS MALT
lymphomas lack any recognizable recurrent chromosomal alteration. Currently
there is very limited data on the mutational landscape of SS and non-SS MALT
lymphoma (3). These studies so far indicate that TNFAIP3, a regulator of the
NF-kB pathway might play a role in the pathogenesis of MALT lymphomas.
Study objective
1. We will perform an exploratory study using whole exome sequencing (WES) on
SS MALT lymphoma samples to pick up specific gene mutations enriched or
exclusively present in salivary MALT lymphoma in SS patients.
2 .We will investigate the relation between mutational load and SS disease
activity and whether there is enrichment for deleterious mutations in patients
with a high SS activity as compared to low SS activity.
3. We will perform (targeted) exome sequencing on repetitive tumor samples of
patients to evaluate clonal evolution in order to detect deleterious mutations
early in the course of the disease in minor sub clones.
Study design
Mutational analysis will be performed on a pilot serie of 10-15 patients using
next generation sequencing of tumor samples and germline DNA. If specific
mutations are found the research will be extended to 30 patients to validate
the incidence of these mutations within the MALT lymphoma patients.
Study burden and risks
No risk for participating patients.
Hanzeplein 1
Groningen 9700RB
NL
Hanzeplein 1
Groningen 9700RB
NL
Listed location countries
Age
Inclusion criteria
Patients previously diagnosed with a MALT lymphoma
Exclusion criteria
n.a.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
Register | ID |
---|---|
CCMO | NL58950.042.16 |