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The genomics of neuroblastoma tumors

 

Tommy Martinsson

Contact Information | List of Publications

Neuroblastoma (NB) is a childhood malignancy of the sympathetic nervous system with heterogeneous clinobiological features. Patients with high-risk neuroblastoma have a very poor prognosis despite aggressive and multi-modal therapy, emphasizing the need for improved treatment and treatment alternatives for these patients. The intensive treatment that commonly includes high-dose chemotherapy, radiation and surgery is also very demanding on the young child with sometimes severe side effects even when the patient survives. Therefore, it is of great clinical interest to study biological and genetic parameters that could further improve treatment and outcome for NB patients.

Figure 1. Tentative framework for the future of neuroblastoma treatment with individualized therapy. The development of new ALK inhibitors will lead to a leap in treatment success rate of aggressive NB tumors. However, since only a fraction of aggressive NB harbors ALK activating mutations in the TK-domain or amplification, there is still need for additional improvement in order to increase the current overall survival of ~65 % in 11q-deleted and MYCN- amplified tumors. Through our study we intend to define which patient group that will benefit from ALK-targeted therapy and identify targets that opt for a combinatorial treatment regime and a more tailored therapy based on the genetic background of patient and tumor.


 

The overall goal of this project is to aid in the identification of new biomarkers, new drug targets, minimize risks and ultimately improve the treatment and survival of NB patients. Knowledge about the fundamental genetic alterations that are associated with variable tumor behavior and patient outcome will lead to more precise prognostication and improved treatment strategies (Fig.1). From a clinical point of view it is also important to define the functional nature of the various mutations for NB patients – e.g. in genes ALK, ATRX and TERT to adjust treatment correctly. Our collaborative effort aims to improve biological understanding and clinical management and therapy for children through NB-based on studies of the genetic make-up as we envision a future were the neuroblastoma patients receive treatment that is tailored according their genetic background, initial risk group and risk of relapse/metastasis. The unique tumor material is characterized by different genetic and genomic methods such as Affymetrix high density SNP microarrays, exons sequencing and whole genome sequencing. Our goal is to understand the molecular mechanisms behind NB and the resulting implications from Biological understanding to Clinical care.

Group members

Tommy Martinsson, PhD, professor, P.I. group leader
Susanne Fransson, PhD, Research Assistant, Post-doc
Malin Östensson, PhD, Post-doc
Niloufar Javanmardi, PhD student
Angela Martinez-Monleon, PhD student
Anna Djos, Assistant Researcher, Biologist,
Rose-Marie Sjöberg, Assistant Researcher, BMA
Anna-Maria Denes, Assistant Researcher
 

Collaborations

We have a strong collaboration with the co-workers in the NNBCR Consortium:

Prof. Bengt Hallberg, GU
Prof. Ruth Palmer, GU
Prof. Chandrasekhar Kanduri, GU
Assoc Prof. Erik Larsson Lekholm, GU
Prof. Per Kogner, KI
Assoc Prof. John-Inge Johnsen, KI

as well as with clinician coworkers

Dr. Jonas Abrahamsson, Drottning Silvia Chidrens Hospital, Göteborg
Dr. Ingrid Öra, Lund hospital
 

Sidansvarig: Dan Baeckström|Sidan uppdaterades: 2016-09-29
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