Publikationsdatum:
2014-12-06
Beschreibung:
Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of diseases with poor prognosis and no standard therapy due to widely varying responses to treatments, thus new therapeutic targets need to be identified. Gene expression profiling (GEP) has helped to separate classes of these diseases to predict survival. Recent genetic studies on the two most common subtypes of PTCL in the Western world, angioimmunoblastic T-cell lymphoma (AITL) and PTCL, not otherwise specified (PTCL-NOS), have revealed recurrent mutations in the epigenetic modifiers TET2, IDH2, and DNMT3A; in the small GTPase RHOA; and rarely in the T-cell receptor (TCR) adaptor protein FYN. Because TCR stimulation is necessary for normal T-cell expansion, activating mutations in the stimulation (CD3/TCR) and costimulation (CD28) pathways could be involved in malignant lymphopoiesis. We performed whole-transcriptome sequencing on a small set of primary PTCL cases and found mutations in CD28, including an aspartate 124 mutation within a fusion transcript between CD28 and family member ICOS as well as a threonine 195 mutation. On targeted re-sequencing of 92 PTCL cases, we found two AITL cases and one ALK- anaplastic large cell lymphoma case with an aspartate 124 mutation (variant frequencies [VF]: 1.03% to 5.90%). We also found mutations at threonine 195 (two AITL, one PTCL-NOS, Tbx21 subtype; VF: 2.90% to 12.30%). Additionally, we found two recurrent mutations with low variant frequencies (
Print ISSN:
0006-4971
Digitale ISSN:
1528-0020
Thema:
Biologie
,
Medizin
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