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Johansson, Gunnar
Publications (10 of 16) Show all publications
Andersson, U., Degerman, S., Dahlin, A. M., Wibom, C., Johansson, G., Bondy, M. L. & Melin, B. S. (2019). The association between longer relative leukocyte telomere length and risk of glioma is independent of the potentially confounding factors allergy, BMI, and smoking. Cancer Causes and Control, 30(2), 177-185
Open this publication in new window or tab >>The association between longer relative leukocyte telomere length and risk of glioma is independent of the potentially confounding factors allergy, BMI, and smoking
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2019 (English)In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 30, no 2, p. 177-185Article in journal (Refereed) Published
Abstract [en]

Purpose: Previous studies have suggested an association between relative leukocyte telomere length (rLTL) and glioma risk. This association may be influenced by several factors, including allergies, BMI, and smoking. Previous studies have shown that individuals with asthma and allergy have shortened relative telomere length, and decreased risk of glioma. Though, the details and the interplay between rLTL, asthma and allergies, and glioma molecular phenotype is largely unknown. Methods: rLTL was measured by qPCR in a Swedish population-based glioma case–control cohort (421 cases and 671 controls). rLTL was related to glioma risk and health parameters associated with asthma and allergy, as well as molecular events in glioma including IDH1 mutation, 1p/19q co-deletion, and EGFR amplification. Results: Longer rLTL was associated with increased risk of glioma (OR = 1.16; 95% CI 1.02–1.31). Similar to previous reports, there was an inverse association between allergy and glioma risk. Specific, allergy symptoms including watery eyes was most strongly associated with glioma risk. High body mass index (BMI) a year prior diagnosis was significantly protective against glioma in our population. Adjusting for allergy, asthma, BMI, and smoking did not markedly change the association between longer rLTL and glioma risk. rLTL among cases was not associated with IDH1 mutation, 1p/19q co-deletion, or EGFR amplification, after adjusting for age at diagnosis and sex. Conclusions: In this Swedish glioma case–control cohort, we identified that long rLTL increases the risk of glioma, an association not confounded by allergy, BMI, or smoking. This highlights the complex interplay of the immune system, rLTL and cancer risk.

Place, publisher, year, edition, pages
Springer, 2019
Keywords
Glioma, Relative leukocyte telomere length (rLTL), Allergy, BMI, Smoking, IDH1, 1p/19q, EGFR
National Category
Cancer and Oncology Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-157597 (URN)10.1007/s10552-018-1120-2 (DOI)000459153800007 ()30560391 (PubMedID)
Available from: 2019-03-28 Created: 2019-03-28 Last updated: 2019-03-28Bibliographically approved
Wu, W.-Y. Y., Johansson, G., Wibom, C., Brännström, T., Malmström, A., Henriksson, R., . . . Melin, B. S. (2019). The Genetic Architecture of Gliomagenesis-Genetic Risk Variants Linked to Specific Molecular Subtypes. Cancers, 11(12), Article ID 2001.
Open this publication in new window or tab >>The Genetic Architecture of Gliomagenesis-Genetic Risk Variants Linked to Specific Molecular Subtypes
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2019 (English)In: Cancers, ISSN 2072-6694, Vol. 11, no 12, article id 2001Article, review/survey (Refereed) Published
Abstract [en]

Genome-wide association studies have identified 25 germline genetic loci that increase the risk of glioma. The somatic tumor molecular alterations, including IDH-mutation status and 1p/19q co-deletion, have been included into the WHO 2016 classification system for glioma. To investigate how the germline genetic risk variants correlate with the somatic molecular subtypes put forward by WHO, we performed a meta-analysis that combined findings from 330 Swedish cases and 876 controls with two other recent studies. In total, 5,103 cases and 10,915 controls were included. Three categories of associations were found. First, variants in TERT and TP53 were associated with increased risk of all glioma subtypes. Second, variants in CDKN2B-AS1, EGFR, and RTEL1 were associated with IDH-wildtype glioma. Third, variants in CCDC26 (the 8q24 locus), C2orf80 (close to IDH), LRIG1, PHLDB1, ETFA, MAML2 and ZBTB16 were associated with IDH-mutant glioma. We therefore propose three etiopathological pathways in gliomagenesis based on germline variants for future guidance of diagnosis and potential functional targets for therapies. Future prospective clinical trials of patients with suspicion of glioma diagnoses, using the genetic variants as biomarkers, are necessary to disentangle how strongly they can predict glioma diagnosis.

Place, publisher, year, edition, pages
MDPI, 2019
Keywords
glioma, IDH mutant, 1p/19q co-deletion, gliomagenesis, genotype phenotype, etiopathogenesis
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-167615 (URN)10.3390/cancers11122001 (DOI)000507382100178 ()31842352 (PubMedID)2-s2.0-85076550363 (Scopus ID)
Available from: 2020-02-06 Created: 2020-02-06 Last updated: 2020-04-08Bibliographically approved
Johansson, G., Brännström, T., Andersson, U., Golovleva, I. & Melin, B. (2017). Molecular classification of malignat glioma. Paper presented at 5th Quadrennial Meeting of the World-Federation-of-Neuro-Oncology-Societies (WFNOS), Zurich, Switzerland, May 4-7, 2017. Neuro-Oncology, 19(S3), 88-88, Article ID P10.15.
Open this publication in new window or tab >>Molecular classification of malignat glioma
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2017 (English)In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 19, no S3, p. 88-88, article id P10.15Article in journal, Meeting abstract (Refereed) Published
Abstract [en]

Background: Malignant glioma are devastating tumors with poor prognosis. In recent years, the classification of glioma have evolved greatly due to exploration of several molecular tools in addition to the traditional immunohistochemistry.

Methods: To further evolve this classification, we thoroughly characterized the molecular and histological signature of 367 glioma patients from Sweden. We first obtained the full medical history and histological classification, along with matched blood samples and unstained tissue slides. We have performed extensive molecular characterization using genome wide association studies, methylation arrays and telomere length assays. We have extended the classification to include IDH1 mutations, chromosome 1p/19q co-deletion, EGFR amplification as well as the expression of two novel cell signaling regulators. The statistical analysis is ongoing and will reveal how well we can classify the tumors by combining the above mentioned techniques. 

Results: As expected we found EGFR upregulation in almost 50% of the patients with glioblastoma and one third of patients with anaplastic astrocytoma and anaplastic oligodendroglioma. No EGFR expression was found in any patient with low grade glioma. In consistence with previous studies 70% of the IDH1 mutated oligodendroglioma had 1p/19q co-deletion. In the IDH1 wildtype oligodendroglioma, about 50% of the low grade tumors had 1p/19q co-deletion. Interestingly, we found complete 1p/19q co-deletion in about 10% of the IDH1 wild type glioblastoma.

Conclusion: Today, 1p/19q co-deletion is normally only studied in suspected oligodendroglioma and not in all types of glioma. Pending the clinical relevance of the 1p/19q co-deleted glioblastoma, it might be wise to expand the 1p/19q classification by including all types of glioma.

Place, publisher, year, edition, pages
Oxford University Press, 2017
Keywords
signal transduction, immunohistochemistry, j mutationa, naplastic astrocytoma, glioblastoma, chromosomes, glioma, methylatio, noligodendroglioma, epidermal growth factor receptors, telomere, up-regulation (physiology), medical history, neoplasms, glioma, malignant, anaplastic oligodendroglioma, amplification, genome-wide association study, idh1 gene, low grade glioma
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-136983 (URN)10.1093/neuonc/nox036.333 (DOI)000402732900335 ()
Conference
5th Quadrennial Meeting of the World-Federation-of-Neuro-Oncology-Societies (WFNOS), Zurich, Switzerland, May 4-7, 2017
Note

Volume 19, Supplement 3, 1 May 2017

5th Quadrennial Meeting of the World Federation of Neuro-Oncology Societies (WFNOS), May 4-7, 2017, Zurich, Switzerland

Available from: 2017-06-30 Created: 2017-06-30 Last updated: 2020-05-18Bibliographically approved
Johansson, G., Andersson, U. & Melin, B. (2016). Recent developments in brain tumor predisposing syndromes. Acta Oncologica, 55(4), 401-411
Open this publication in new window or tab >>Recent developments in brain tumor predisposing syndromes
2016 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, no 4, p. 401-411Article, review/survey (Refereed) Published
Abstract [en]

The etiologies of brain tumors are in the most cases unknown, but improvements in genetics and DNA screening have helped to identify a wide range of brain tumor predisposition disorders. In this review we are discussing some of the most common predisposition disorders, namely: neurofibromatosis type 1 and 2, schwannomatosis, rhabdoid tumor predisposition disorder, nevoid basal cell carcinoma syndrome (Gorlin), tuberous sclerosis complex, von Hippel-Lindau, Li-Fraumeni and Turcot syndromes. Recent findings from the GLIOGENE collaboration and the newly identified glioma causing gene POT1, will also be discussed. Genetics. We will describe these disorders from a genetic and clinical standpoint, focusing on the difference in clinical symptoms depending on the underlying gene or germline mutation. Central nervous system (CNS) tumors. Most of these disorders predispose the carriers to a wide range of symptoms. Herein, we will focus particularly on tumors affecting the CNS and discuss improvements of targeted therapy for the particular disorders.

Place, publisher, year, edition, pages
Taylor & Francis, 2016
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-119059 (URN)10.3109/0284186X.2015.1107190 (DOI)000372125400001 ()26634384 (PubMedID)
Available from: 2016-04-22 Created: 2016-04-11 Last updated: 2018-06-07Bibliographically approved
Patel, A. V., Johansson, G., Colbert, M. C., Dasgupta, B. & Ratner, N. (2015). Fatty acid synthase is a metabolic oncogene targetable in malignant peripheral nerve sheath tumors. Neuro-Oncology, 17(12), 1599-1608
Open this publication in new window or tab >>Fatty acid synthase is a metabolic oncogene targetable in malignant peripheral nerve sheath tumors
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2015 (English)In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 17, no 12, p. 1599-1608Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are soft tissue sarcomas with minimal therapeutic opportunities. We observed that lipid droplets (LDs) accumulate in human MPNST cell lines and in primary human tumor samples. The goal of this study was to investigate the relevance of lipid metabolism to MPNST survival and as a possible therapeutic target.

METHODS: Based on preliminary findings that MPNSTs accumulate LDs, we hypothesized that a deregulated lipid metabolism supports MPNST cell survival/proliferation rate. To test this, we examined respiration, role of fatty acid oxidation (FAO), and the enzyme fatty acid synthase involved in de novo fatty acid synthesis in MPNSTs using both genetic and pharmacological tools.

RESULTS: We demonstrate that LDs accumulate in MPNST cell lines, primary human and mouse MPNST tumors, and neural crest cells. LDs from MPNST cells disappear on lipid deprivation, indicating that LDs can be oxidized as a source of energy. Inhibition of FAO decreased oxygen consumption and reduced MPNST survival, indicating that MPNST cells likely metabolize LDs through active FAO. FAO inhibition reduced oxygen consumption and survival even in the absence of exogenous lipids, indicating that lipids synthesized de novo can also be oxidized. Consequently, inhibition of de novo fatty acid synthesis, which is overexpressed in human MPNST cell lines, effectively reduced MPNST survival and delayed induction of tumor growth in vivo.

CONCLUSION: Our results show that MPNSTs depend on lipid metabolic pathways and suggest that disrupting lipid metabolism could be a potential new strategy for the development of MPNST therapeutics.

Keywords
Animals, Antineoplastic Agents/*therapeutic use, Cell Death, Cell Line, Tumor, *Drug Screening Assays, Antitumor, Humans, Immunosuppressive Agents/therapeutic use, Mice, Mice, Nude, Nerve Sheath Neoplasms/*drug therapy/metabolism, Protein Kinases/*metabolism, Quinazolines/pharmacology, Ribosomal Protein S6 Kinases, 70-kDa/metabolism, Signal Transduction, Sirolimus/*analogs & derivatives/therapeutic use, TOR Serine-Threonine Kinases, Up-Regulation
National Category
Cell Biology
Identifiers
urn:nbn:se:umu:diva-106956 (URN)10.1093/neuonc/nov076 (DOI)000368452700008 ()26116612 (PubMedID)
Available from: 2015-08-13 Created: 2015-08-13 Last updated: 2018-06-07Bibliographically approved
Chen, C.-K., Yang, C.-Y., Hua, K.-T., Hua, K.-T., Ho, M.-C., Johansson, G., . . . Kuo, M.-L. (2014). Leukocyte cell-derived chemotaxin 2 antagonizes MET receptor activation to suppress hepatocellular carcinoma vascular invasion by protein tyrosine phosphatase 1B recruitment. Hepatology, 59(3), 974-985
Open this publication in new window or tab >>Leukocyte cell-derived chemotaxin 2 antagonizes MET receptor activation to suppress hepatocellular carcinoma vascular invasion by protein tyrosine phosphatase 1B recruitment
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2014 (English)In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 59, no 3, p. 974-985Article in journal (Refereed) Published
Abstract [en]

UNLABELLED: Leukocyte cell-derived chemotoxin 2 (LECT2) has been shown to act as a tumor suppressor in hepatocellular carcinoma (HCC). However, the underlying mechanism has not yet been completely defined. Here, we employ a LECT2-affinity column plus liquid chromatography coupled with tandem mass spectrometry to identify LECT2-binding proteins and found that MET receptor strongly interacted with LECT2 protein. Despite the presence of hepatocyte growth factor, the LECT2 binding causes an antagonistic effect to MET receptor activation through recruitment of protein tyrosine phosphatase 1B. The antagonistic effect of LECT2 on MET activation also mainly contributes to the blockage of vascular invasion and metastasis of HCC. Furthermore, serial deletions and mutations of LECT2 showed that the HxGxD motif is primarily responsible for MET receptor binding and its antagonistic effects.

CONCLUSION: These findings reveal a novel, specific inhibitory function of LECT2 in HCC by the direct binding and inactivation of MET, opening a potential avenue for treating MET-related liver cancer.

Place, publisher, year, edition, pages
Hoboken: Wiley-Blackwell, 2014
Keywords
amino acid sequence, beta-catenin, C-MET, growth, expression, kinase, target, LECT2, tumor, purification
National Category
Cell Biology
Identifiers
urn:nbn:se:umu:diva-106962 (URN)10.1002/hep.26738 (DOI)000331787500027 ()24114941 (PubMedID)
Available from: 2015-08-13 Created: 2015-08-13 Last updated: 2018-09-10Bibliographically approved
Johansson, G., Peng, P.-C., Huang, P.-Y., Chien, H.-F., Hua, K.-T., Kuo, M.-L., . . . Lee, M.-J. (2014). Soluble AXL: a possible circulating biomarker for neurofibromatosis type 1 related tumor burden. PLoS ONE, 9(12), Article ID e115916.
Open this publication in new window or tab >>Soluble AXL: a possible circulating biomarker for neurofibromatosis type 1 related tumor burden
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2014 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 12, article id e115916Article in journal (Refereed) Published
Abstract [en]

Neurofibromatosis type 1 (NF1) is the most common tumor predisposition disorder affecting 1/3500 worldwide. Patients are at risk of developing benign (neurofibromas) and malignant peripheral nerve sheath tumors (MPNST). The AXL receptor tyrosine kinase has been implicated in several kinds of cancers, but so far no studies have investigated the role of AXL in NF1 related tumorigenesis. Recently, the soluble fraction from the extracellular domain of AXL (sAXL) has been found in human plasma, and its level was correlated to poor prognosis in patients with renal cancer. Compared to normal human Schwann cells, a significantly high expression level of AXL was found in three of the four MPNST cell lines and two of the three primary MPNST tissues. Similarly, the level of sAXL in conditioned media corresponded to the protein and mRNA levels of AXL in the MPNST cell lines. Furthermore, in two different human MPNST xenograft models, the human sAXL could be detected in the mouse plasma. Its level was proportionate to the size of the xenograft tumors, while no human sAXL was detect prior to the formation of the tumors. Treatment with a newly developed photodynamic therapy, prevented further tumor growth and resulted in drastically reduced the levels of sAXL compared to that of the control group. Finally, the level of sAXL was significantly increased in patients with plexiform tumors compared to patients with only dermal neurofibromas, further supporting the role of sAXL as a marker for NF1 related tumor burden.

Place, publisher, year, edition, pages
San Francisco: Public Library of Science, 2014
Keywords
nerve sheath tumors, receptor tyrosine kinase, growth factor, Schwann cells, photodynamic inactivation, ovarian cancer, in vitro, expression, invasion, GAS6
National Category
Cell Biology
Identifiers
urn:nbn:se:umu:diva-106961 (URN)10.1371/journal.pone.0115916 (DOI)000347119100076 ()25551830 (PubMedID)
Available from: 2015-08-13 Created: 2015-08-13 Last updated: 2018-09-10Bibliographically approved
Su, J.-L., Chen, P.-S., Johansson, G. & Kuo, M.-L. (2012). Function and regulation of let-7 family microRNAs. MicroRNA (Shāriqah, United Arab Emirates), 1(1), 34-39
Open this publication in new window or tab >>Function and regulation of let-7 family microRNAs
2012 (English)In: MicroRNA (Shāriqah, United Arab Emirates), ISSN 2211-5366, Vol. 1, no 1, p. 34-39Article in journal (Refereed) Published
Abstract [en]

MicroRNAs (miRNAs) are a group of small noncoding RNAs capable of regulating specific gene expression. Let-7 miRNA was first discovered in Caenorhabditis elegans and it is highly conserved in human tissues. The human let- 7 family of miRNA contains 12 members of miRNA. Today, these members have become the most studied miRNAs and they have attracted attention of researchers in various fields, such as development, stem cell biology, aging, and metabolism. Furthermore, there is a large body of evidence linking the loss of let-7 expression and the development of poorly differentiated, aggressive cancers. In addition to the canonical biogenesis pathway, let-7 has been found to be regulated by protein factors, such as RNA binding proteins previously identified as regulators of protein-coding mRNAs. Moreover, the direct interaction between miRNAs has recently been identified as a novel pathway to control let-7 expression. In this review, we discuss the multifaceted roles of let-7 and provide an overview of its regulation at multiple levels.

Place, publisher, year, edition, pages
Bentham, 2012
National Category
Cell Biology
Identifiers
urn:nbn:se:umu:diva-106963 (URN)10.2174/2211536611201010034 (DOI)25048088 (PubMedID)
Available from: 2015-08-13 Created: 2015-08-13 Last updated: 2019-02-26Bibliographically approved
Wood, M., Rawe, M., Johansson, G., Pang, S., Soderquist, R. S., Patel, A. V., . . . Sanchez, Y. (2011). Discovery of a small molecule targeting IRA2 deletion in budding yeast and neurofibromin loss in malignant peripheral nerve sheath tumor cells. Molecular Cancer Therapeutics, 10(9), 1740-1750
Open this publication in new window or tab >>Discovery of a small molecule targeting IRA2 deletion in budding yeast and neurofibromin loss in malignant peripheral nerve sheath tumor cells
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2011 (English)In: Molecular Cancer Therapeutics, ISSN 1535-7163, E-ISSN 1538-8514, Vol. 10, no 9, p. 1740-1750Article in journal (Refereed) Published
Abstract [en]

Malignant peripheral nerve sheath tumor (MPNST) is a life-threatening complication of neurofibromatosis type 1 (NF1). NF1 is caused by mutation in the gene encoding neurofibromin, a negative regulator of Ras signaling. There are no effective pharmacologic therapies for MPNST. To identify new therapeutic approaches targeting this dangerous malignancy, we developed assays in NF1(+/+) and NF1(-/-) MPNST cell lines and in budding yeast lacking the NF1 homologue IRA2 (ira2Δ). Here, we describe UC1, a small molecule that targets NF1(-/-) cell lines and ira2Δ budding yeast. By using yeast genetics, we identified NAB3 as a high-copy suppressor of UC1 sensitivity. NAB3 encodes an RNA binding protein that associates with the C-terminal domain of RNA Pol II and plays a role in the termination of nonpolyadenylated RNA transcripts. Strains with deletion of IRA2 are sensitive to genetic inactivation of NAB3, suggesting an interaction between Ras signaling and Nab3-dependent transcript termination. This work identifies a lead compound and a possible target pathway for NF1-associated MPNST, and shows a novel model system approach to identify and validate target pathways for cancer cells in which NF1 loss drives tumor formation.

Place, publisher, year, edition, pages
American Association for Cancer Research, 2011
National Category
Cell Biology
Identifiers
urn:nbn:se:umu:diva-106957 (URN)10.1158/1535-7163.MCT-11-0309 (DOI)000294668900021 ()21697395 (PubMedID)
Funder
NIH (National Institute of Health), R21NS060940NIH (National Institute of Health), T32-CA009658-18
Available from: 2015-08-13 Created: 2015-08-13 Last updated: 2019-01-30Bibliographically approved
Hua, K.-T., Tan, C.-T., Johansson, G., Lee, J.-M., Yang, P.-W., Lu, H.-Y., . . . Kuo, M.-L. (2011). N-α-acetyltransferase 10 protein suppresses cancer cell metastasis by binding PIX proteins and inhibiting Cdc42/Rac1 activity. Cancer Cell, 19(2), 218-231
Open this publication in new window or tab >>N-α-acetyltransferase 10 protein suppresses cancer cell metastasis by binding PIX proteins and inhibiting Cdc42/Rac1 activity
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2011 (English)In: Cancer Cell, ISSN 1535-6108, E-ISSN 1878-3686, Vol. 19, no 2, p. 218-231Article in journal (Refereed) Published
Abstract [en]

N-α-acetyltransferase 10 protein, Naa10p, is an N-acetyltransferase known to be involved in cell cycle control. We found that Naa10p was expressed lower in varieties of malignancies with lymph node metastasis compared with non-lymph node metastasis. Higher Naa10p expression correlates the survival of lung cancer patients. Naa10p significantly suppressed migration, tumor growth, and metastasis independent of its enzymatic activity. Instead, Naa10p binds to the GIT-binding domain of PIX, thereby preventing the formation of the GIT-PIX-Paxillin complex, resulting in reduced intrinsic Cdc42/Rac1 activity and decreased cell migration. Forced expression of PIX in Naa10-transfected tumor cells restored the migration and metastasis ability. We suggest that Naa10p functions as a tumor metastasis suppressor by disrupting the migratory complex, PIX-GIT- Paxillin, in cancer cells.

Place, publisher, year, edition, pages
Cell Press, 2011
National Category
Cell Biology
Identifiers
urn:nbn:se:umu:diva-106964 (URN)10.1016/j.ccr.2010.11.010 (DOI)21295525 (PubMedID)
Available from: 2015-08-13 Created: 2015-08-13 Last updated: 2019-01-30Bibliographically approved
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