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High Resolution Imaging of Mitotic Segregation Errors, Genetic Diversity, and Differentiation Hierarchies in Childhood Solid Tumors

Principal investigator; Gisselsson Nord, David, Associate Professor, MD/PhD

Clinical speciality: Pathology

Phone: +4646-173418

Co-workers: Yuesheng Jin (PhD), Linda Holmquist Mengelbier (PhD), Ingrid Öra (Sr Consultant, Assoc Prof), Tord Jonson (PhD), Jenny Karlsson (PhD)

Research area/areas: Cancer and Oncology, Medical Genetics, Pediatrics

Our group is dedicated to understanding the transition from normal tissues to invasive cancer. Our primary study target is childhood tumours and the ultimate aim of our research is to produce better methods for risk stratification of children with cancer in order to optimize treatment. We use a combination of novel genomic techniques (SNP array-based CGH) and high resolution microscopy (FISH, AFM, immunofluorescence) to map genetic and phenotypic variation within individual tumours, complemented by in vitro systems for detailed three-dimensional analysis of chromosome segregation patterns.

In collaboration with pathologists, physicists and mathematicians we have developed techniques for simultaneous assessment of abnormal chromosome segregation and protein expression in single tumour cells and in histopathological tissue sections.

These parameters will be used in conjunction with clinical data in an attempt to answer the following questions: (1) Do mitotic segregation errors correlate to genetic and immunophenotypic intra-tumour diversity in vivo? (2) Is genomic instability present in all cells in a tumour, or is it confined to cell populations at a specific differentiation level? (3) Can the frequency of chromosome segregation errors or the degree of genomic/immunophenotypic intra-tumour diversity be used to improve clinical risk stratification?

Improved risk stratification of children with cancer will contribute to a more individualised therapy, avoiding over treatment of children with low-risk tumours and under-treatment of children with high-risk tumours. Knowledge of the process behind genetic diversity and evolution of cancer cells may help us understand the mechanisms behind treatment failure and relapse.

Link to project homepage: http://www.med.lu.se/labmedlund/clinical_genetics/research/david_gisselsson_nord

5 recent original publications

Gisselsson D, Jin Y, Lindgren D, Persson J, Gisselsson L, Hanks S, Sehic D, Holmquist Mengelbier L, Öra I, Rahman N, Mertens F, Mitelman F, Mandahl N
Generation of trisomies in cancer cells by multipolar mitosis and incomplete cytokinesis
Proc Natl Acad Sci USA. 2010; Epub ahead of print.:

Mengelbier LH, Karlsson J, Lindgren D, Ora I, Isaksson M, Frigyesi I, Frigyesi A, Bras J, Sandstedt B, Gisselsson D.
Deletions of 16q in Wilms Tumors Localize to Blastemal-Anaplastic Cells and Are Associated with Reduced Expression of the IRXB Renal Tubulogenesis Gene Cluster.
Am J Pathol. 2010; 177: 2609-21

Gisselsson D, Lindgren D, Mengelbier LH, Ora I, Yeger H.
Genetic bottlenecks and the hazardous game of population reduction in cell line based research
Exp Cell Res. 2010; Epub ahead of print.:

Gisselsson D
Mechanisms of whole chromosome gains in tumours – many answers to a simple question
Cytogenet Genome Res. 2010; in press:

Gisselsson D, Håkanson U, Stoller P, Rosengren A, Stewénius Y, Kahl F, Panagopoulos I.
When the genome plays dice: circumvention of the spindle assembly checkpoint and near-random chromosome segregation in multipolar cancer cell mitoses.
PLoS ONE. 2008; 3: e1871

Further publications here (new window)

Financing/year