Role of the p53 pathway and DNA damage response in clonal heterogeneity of ALK+ ALCL


Masaryk University

Sarka Pospisilova

Supervisor

Publication Link

Genomics of lymphoproliferative disorders; role of p53 abnormalities in cancer

Research Interest

Prof. S. Pospisilova is head of the research center of Molecular Medicine in CEITEC, MU and also works in the department of Internal Medicine – Hematology and Oncology in the University Hospital Brno. She coordinates national and international research projects in leukaemia and lymphoma and is a member of the board of the European Research Initiative on CLL (ERIC) within the European Leukaemia Net. Her research group studies the genomic background of ALK-related malignancies (with application of NGS and array technologies) and the role of the p53 pathway and microRNAs in these tumours.
Characterization of ALK role in paediatric tumours specifically in neuroblastoma and rhabdomyosarcoma. Introduction of high-throughput analyses of human genomes for diagnostic tests.Study of neuroblastoma and other paediatric CNV (copy number variation) malignancies as epigenetic diseases with aim to better understand role of epigenome in ALK-induced malignancies in general. Identification of potential therapeutic targets in relapsed or refractory paediatric malignancies applicable in clinical practice.

Cosimo Lobello

Research student

ORCID Link

 

Research Interest

I am Cosimo Lobello and I come from Italy. I will study in the team of Prof. Sarka Pospisilova in CEITEC. I have completed a Master’s degree in Medical Biotechnologies at the University of Perugia (Italy). I am fascinated by human complexity, both in terms of its greatness as well as its smallness in the face of diseases or incurable cancers. I chose to study the application of biology in the medical field, in particular in genetics, and I want to study this field because I am driven by a curiosity and by a need to understand the mechanisms that are behind such phenomena. I have always been deeply interested in the new methods and technologies involved in biology, Next Generation Sequencing, SNP-array and so on.

Research description

The p53 pathway and DNA damage response (DDR) is frequently abrogated in many tumours including lymphoproliferative disorders. To describe the genetiv features and understand the biology of ALK+ALCL, we plan to analyze the functionality of the pathway at genomic and proteomic levels (including p53 upstream and downstream genes and microRNAs).

Fresh frozen serial samples collected from ALCL patients and also tissue microarray from FFPE blocks will be used. Optionally, fine needle biopsies of lymph nodes taken under ultrasonography control could be used as a source of material for further analysis. These techniques would help to identify the potential impact of genetic changes in tumour and healthy cells and also the realtionshio to clinical behavior of ALCL.

Expected Results:
To report genetic and epigenetic changes related to p53 and DDR pathways in ALK+ ALCL and to correlate them with clinical behavior of lymphoma patients 

Planned secondment(s):
Year 1: TissueGnostics (PO#2) – development of tissue microarrays and analysis of histomorphology – 2 month;
Year 2: UGOT (B#12) – to access novel model systems including Drospohila for the analysis of DNA damage pathways – 2 months.

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