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Hansson, Magnus
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Publications (4 of 4) Show all publications
Fransson, S., Hansson, M., Ruuth, K., Djos, A., Berbegall, A., Javanmardi, N., . . . Martinsson, T. (2015). Intragenic Anaplastic Lymphoma Kinase (ALK) Rearrangements: Translocations as a Novel Mechanism of ALK Activation in Neuroblastoma Tumors. Genes, Chromosomes and Cancer, 54(2), 99-109
Open this publication in new window or tab >>Intragenic Anaplastic Lymphoma Kinase (ALK) Rearrangements: Translocations as a Novel Mechanism of ALK Activation in Neuroblastoma Tumors
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2015 (English)In: Genes, Chromosomes and Cancer, ISSN 1045-2257, E-ISSN 1098-2264, Vol. 54, no 2, p. 99-109Article in journal (Refereed) Published
Abstract [en]

Anaplastic lymphoma kinase (ALK) has been demonstrated to be deregulated in sporadic as well as in familiar cases of neuroblastoma (NB). Whereas ALK-fusion proteins are common in lymphoma and lung cancer, there are few reports of ALK rearrangements in NB indicating that ALK mainly exerts its oncogenic capacity via activating mutations and/or overexpression in this tumor type. In this study, 332 NB tumors and 13 cell lines were screened by high resolution single nucleotide polymorphism microarray. Gain of 2p was detected in 23% (60/332) of primary tumors and 46% (6/13) of cell lines, while breakpoints at the ALK locus were detected in four primary tumors and two cell lines. These were further analyzed by next generation sequencing and a targeted enrichment approach. Samples with both ALK and MYCN amplification displayed complex genomic rearrangements with multiple breakpoints within the amplicon. None of the translocations characterized in primary NB tumors are likely to result in a chimeric protein. However, immunohistochemical analysis reveals high levels of phosphorylated ALK in these samples despite lack of initial exons, possibly due to alternative transcription initiation sites. Both ALK proteins predicted to arise from such alterations and from the abnormal ALK exon 4-11 deletion observed in the CLB-BAR cell line show strong activation of downstream targets STAT3 and extracellular signal-regulated kinase (ERK) when expressed in PC12 cells. Taken together, our data indicate a novel, although rare, mechanism of ALK activation with implications for NB tumorigenesis. 

National Category
Cancer and Oncology Medical Genetics
Identifiers
urn:nbn:se:umu:diva-99211 (URN)10.1002/gcc.22223 (DOI)000346348600005 ()
Available from: 2015-04-22 Created: 2015-02-04 Last updated: 2018-06-07Bibliographically approved
Andersson, C., Österlundh, G., Enlund, F., Kindblom, L.-G. & Hansson, M. (2014). Primary spinal intradural mesenchymal chondrosarcoma with detection of fusion gene HEY1-NCOA2: a paediatric case report and review of the literature. Oncology Letters, 8(4), 1608-1612
Open this publication in new window or tab >>Primary spinal intradural mesenchymal chondrosarcoma with detection of fusion gene HEY1-NCOA2: a paediatric case report and review of the literature
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2014 (English)In: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 8, no 4, p. 1608-1612Article, review/survey (Refereed) Published
Abstract [en]

Mesenchymal chondrosarcoma is an extremely rare malignant tumour that most commonly originates in the bone, but is also present in extraskeletal sites. The tumour is morphologically characterized by a biphasic pattern of small round cells and islands of cartilage. Spinal mesenchymal chondrosarcomas are even rarer and, therefore, few investigations exist regarding the biological behaviour of the tumours. In the present study, we report a case of a 10-year-old female presenting with 9 months of back pain and radiographic findings of an intradural lesion measuring 1.5 cm at the level of Th4. The tumour was completely excised and subjected to pathological analyses. Following detection of the HEY1-NCOA2 fusion gene, the tumour was morphologically and immunohistochemically defined as an intradural mesenchymal chondrosarcoma attached to the dura mater. In this study, we validate the recent identification of the fusion gene HEY1-NCOA2 in paediatric extraskeletal mesenchymal chondrosarcomas: The relevant literature is reviewed and further discussed in relation to our findings.

Keywords
chondrosarcoma, bone tumour, intradural, HEY1-NCOA2, fusion gene, sarcoma
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-104157 (URN)10.3892/ol.2014.2364 (DOI)000342725400038 ()
Available from: 2015-06-17 Created: 2015-06-08 Last updated: 2018-06-07Bibliographically approved
Fehr, A., Hansson, M. C., Kindblom, L.-G. & Stenman, G. (2012). YWHAE-FAM22 gene fusion in clear cell sarcoma of the kidney [Letter to the editor]. Journal of Pathology, 227(4), e5-e7
Open this publication in new window or tab >>YWHAE-FAM22 gene fusion in clear cell sarcoma of the kidney
2012 (English)In: Journal of Pathology, ISSN 0022-3417, E-ISSN 1096-9896, Vol. 227, no 4, p. e5-e7Article in journal, Letter (Refereed) Published
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-57743 (URN)10.1002/path.4040 (DOI)000306229100001 ()
Available from: 2012-08-20 Created: 2012-08-14 Last updated: 2018-06-08Bibliographically approved
Martinsson, T., Eriksson, T., Abrahamsson, J., Caren, H., Hansson, M., Kogner, P., . . . Hallberg, B. (2011). Appearance of the novel activating F1174S ALK mutation in neuroblastoma correlates with aggressive tumour progression and unresponsiveness to therapy. Cancer Research, 71(1), 98-105
Open this publication in new window or tab >>Appearance of the novel activating F1174S ALK mutation in neuroblastoma correlates with aggressive tumour progression and unresponsiveness to therapy
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2011 (English)In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 71, no 1, p. 98-105Article in journal (Other academic) Published
Abstract [en]

Mutations in the kinase domain of the ALK kinase have emerged recently as important players in the genetics of the childhood tumor neuroblastoma. Here we report the appearance of a novel ALK mutation in neuroblastoma, correlating with aggressive tumor behaviour. Analyses of genomic DNA from biopsy samples initially showed ALK sequence to be wild type. However, during disease progression mutation of amino acid F1174 to a serine within the ALK kinase domain was observed, which correlated with aggressive neuroblastoma progression in the patient. We show that mutation of F1174 to serine generates a potent gain-of-function mutant, as observed in two independent systems. Firstly, PC12 cell lines expressing ALKF1174S display ligand independent activation of ALK and further downstream signaling activation. Secondly, analysis of ALKF1174S in Drosophila models confirms that the mutation mediates a strong rough eye phenotype upon expression in the developing eye. Thus, we report a novel ALKF1174S mutation, which displays ligand independent activity in vivo, correlating with rapid and treatment resistant tumor growth. The study also shows that initial screening in the first tumor biopsy of a patient may not be sufficient and that further molecular analyses in particular in tumor progression and/or tumor relapse is warranted for better understanding of the treatment of neuroblastoma patients.

Place, publisher, year, edition, pages
American Association for Cancer Research, 2011
Keywords
ALK, neuroblastoma, gain of function
National Category
Cell and Molecular Biology
Research subject
Molecular Biology
Identifiers
urn:nbn:se:umu:diva-36978 (URN)10.1158/0008-5472.CAN-10-2366 (DOI)
Projects
Exploiting Drosophila as a model system for studying Anaplastic Lymphoma Kinase in vivo
Available from: 2010-10-14 Created: 2010-10-14 Last updated: 2018-06-08Bibliographically approved
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