Genetic evolution in recurrent T-cell lymphoma

• Applicant: Dr. Alexandra Butzmann
• Subject Area: Hematology, Oncology
• Term: from 2018 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 404788958

Peripheral T-cell lymphomas (PTCL) are fatal in 60% of the patients, and the prognosis hasn’t changed in the past two decades. This is attributable to a lack of information for classification, risk factors and pathogenesis. Due to the rare prevalence of PTCL, throughout studies, and studies with a higher statistical power are missing. Recent studies show recurrent mutations in the two major sub-type angioimmunoblastic (AITL) and peripheral T-cell lymphoma not otherwise specified (PTCL, NOS), but the clinical impact is unknown. I claim, that a detailed molecular investigation can help understanding these neoplasms and therefor will help to achieve better outcomes for PTCL patients. I want to study the genetic landscape and evolution of the two major sub-groups of PTCL, AITL and PTCL, NOS, by combining important methods of Next Generation Sequencing: Whole Exome Sequencing, exome targeted deep sequencing and whole transcriptome RNA-sequencing. My proposed study consists of two main parts. In the first part I will sequence 37 PTCL samples at diagnosis and recurrence and I will identify common and different mutations at both stages, as well as sub-group specific mutations. Using the results of that first part I will, together with specialist in the field of hematology and hematopathology, design an exome targeted panel and discuss the whole transcriptome RNA-sequencing design. Consequentially, I will conduct exome targeted sequencing and whole transcriptome RNA-sequencing on 123 PTCL samples at diagnosis (n=123) and recurrence (n=86). With modern sequencing technologies, I will be able to identify low allele frequency variants within the tumor samples, that were identified as sensitive markers for prognostication in other cancers. Finally, I will analyze all resulting data, gene expression profiles and genetic landscape, in the context of clinical data, morphologic features and perform a pathway analysis. With analyzing 150 patient samples overall, my proposed study will be the first, that provides an exhaustive overview of the genetic changes happening during progression of PTCL within the clinical context.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Robert S. Ohgami, Ph.D.