Group Göran Stenman

Research Summary

Aims

The overall goals of our research are: (1) to identify and molecularly characterize recurrent fusion oncogenes, mutations, and other genomic rearrangements in glandular tumors of the breast and head and neck; (2) to study the pathogenetic and clinical significance of identified drivers and based on this knowledge develop new targeted cancer therapies; (3) to elucidate the molecular pathogenesis and develop new treatment options for patients with the inherited Brooke-Spiegler tumor syndrome.

Workplan

Genomic and transcriptomic profiles and novel fusion oncogenes and mutations are identified with next generation sequencing technologies and arrayCGH. Clinical and histopathological data are collected and analyzed from all patients. The functions and molecular consequences of identified drivers are studied with molecular and cell biological techniques. Candidate drugs are identified by screening of large drug libraries using validated human tumor models followed by testing in preclinical patient-derived xenograft models and in clinical studies.

Significance

Mapping of the genomic landscape of tumors provides unique opportunities to identify novel fusion oncogenes and mutated cancer genes. Molecular and functional characterization of these yield new knowledge about pathogenetic mechanisms and signaling pathways of importance for tumorigenesis and form the basis for development of new targeted cancer therapies.

Our discovery that the MYB-NFIB fusion oncogene in adenoid cystic carcinoma is regulated by IGF1R via the AKT signaling pathway, and that IGF1R inhibitors in combination with other kinase inhibitors can inhibit tumor growth in vitro and in vivo, is the most recent example of this successful approach. Our novel finding that MYB is an oncogenic driver also in patients with the hereditary Brooke-Spiegler tumor syndrome opens new opportunities to, for the first time, test drug-based treatments on patients with this severe disease.

Our group is also involved in a collaborative project together with researchers at the departments of plastic surgery and clinical genetics where we genetically characterize children with craniofacial malformations.

Research tools and resources

We use state-of-the-art genomics approaches and molecular and cellular biology techniques to identify and functionally characterize genomic changes in human glandular tumors to identify new biomarkers and treatment strategies.

Current group members

Göran Stenman, DMD, PhD, Senior professor
André Fehr, PhD, Staff scientist
Fredrik Jäwert, DDS, PhD, Postdoc, oral and maxillofacial surgeon
Junchi Huang, PhD, Postdoc
Maryam Kakay Afshari, MD, PhD, resident physician in oncology
Therese Carlsson, Technician (part time)

Associated group members

Lars Kölby MD, PhD, Professor, senior consultant, plastic surgeon
Alexandra Topa, MD, PhD student, clinical geneticist
Anna Rohlin, PhD, clinical scientist/geneticist

Selected publications

1. IGF2/IGF1R signaling as a therapeutic target in MYB-positive adenoid cystic carcinomas and other fusion gene driven tumors.
   Andersson MK, Åman P, Stenman G. Cells 2019; 8 (8), 913. doi.org/10.3390/cells8080913.
    
2. Targeting the oncogenic transcriptional regulator MYB in adenoid cystic carcinoma by inhibition of IGF1R-AKT signaling.
   Andersson MK, Afshar MK, Andrén Y, Wick MJ, Stenman G. J Natl Cancer Inst 2017; 109 (9), Sep 1. doi:10.1093/ jnci/djx017.
    
3. Multi-dimensional genomic analysis of myoepithelial carcinoma identifies prevalent oncogenic gene fusions.
   Dalin MG, Katabi N, Persson M, Lee K-W, Makarov V, Desrichard A, Walsh LA, West L, Nadeem Z, Ramaswami D, Havel JJ, Kuo F, Chadalavada K, Nanjangud GJ, Ganly I, Riaz N, Ho AL, Antonescu CR, Ghossein R, Stenman G, Chan TA, Morris LGT. Nat Commun 2017; 8(1):1197, Oct 30. doi: 10.1038/s41467-017-01178-z.
    
4. Overexpression of MYB drives proliferation of CYLD-defective cylindroma cells.
   Rajan N, Andersson MK, Sinclair N, Fehr A, Hodgson K, Lord CJ, Kazakov DV, Vanecek T, Ashworth A, Stenman G. J Pathol 239:197-205, 2016.
    
5. Genomic landscape of adenoid cystic carcinoma of the breast.
   Martelotto LG, De Filippo MR, Ng CH, Natrajan R, Fuhrmann L, Cyrta J, Piscuoglio S, Wen H-C, Lim RS, Schultheis AM, Wen YH, Edelweiss M, Mariani O, Stenman G, Chan TA, Colombo P-E, Norton L, Vincent-Salomon A, Reis-Filho JS, Weigelt B. J Pathol 237:179-89, 2015.
    
6. K5/K14-positive cells contribute to salivary gland-like breast tumors with myoepithelial differentiation.
   Boecker W, Stenman G, Loening T, Andersson MK, Bankfalvi A, von Holstein S, Heegaard S, Lange A, Berg T, Samoilova V, Tiemann K, Buchwalow I. Mod Pathol 26:1086-100, 2013.
    
7. Salivary gland cancer: an update on present and emerging therapies.
   Carlson J, Licitra L, Locati L, Raben D, Persson F, Stenman G. Am Soc Clin Oncol Educ Book 33:257-63, 2013.
    
8. Genomic profiles and CRTC1-MAML2 fusion distinguish different subtypes of mucoepidermoid carcinoma.
   Jee KJ, Persson M, Heikinheimo K, Passador-Santos F, Aro K, Knuutila S, Odell EW, Mäkitie A, Sundelin K, Stenman G, Leivo I. Mod Pathol 26:213-22, 2013.
    
9. The MYB-NFIB gene fusion – a novel genetic link between adenoid cystic carcinoma and dermal cylindroma.
   Fehr A, Kovács A, Löning T, Frierson H Jr, van den Oord J, Stenman G. J Pathol 224:322–327, 2011.
    
10. Recurrent fusion of MYB and NFIB transcription factor genes in carcinomas of the breast and head and neck.
    Persson M, Andrén Y, Mark J, Horlings HM, Persson F, Stenman G. Proc Natl Acad Sci USA 106:18740–18744, 2009.

More group Göran Stenman publications on PubMed