Cancer syndrome/Rasopathy NF1: pathoetiology and epidemiology

​Description of Research

Mutations of NF1 gene cause the neurocutaneous-skeletal-opthtalmologic syndrome neurofibroma-tosis 1 (NF1) with an incidence of about 1:2000. NF1 is also the most common cancer syndrome, and can also be classified as a Rasopathy.  The deficiency of NF1 tumor suppressor / histogenesis factor impairs the development cell-cell or cell-matrix contacts, and calcium-mediated cell signaling. Our research penetrates to the question how a single mutation in the NF1 gene can cause the development of tumor masses, skeletal disfigurement, speech defects, and tumors of the eye and the optic pathway. Many of the phenomena are hormonally regulated, and the hyperactivation of the Ras pathway is reflected to altered drug metabolism. The translational approach from molecules to patients is carried out in the environment including Institute of Biomedicine/Department of Cell Biology and Anatomy, and the Department of Dermatology which hosts the Neurofibromatosis Clinic.


List of Personnel

Heli Ylä-Outinen, MD, PhD, Clinical Teacher
Niina Loponen, MD, University Teacher

PhD Students:
Maria Alanne, MD
Roope Kallionpää, FM
Jussi Leppävirta, MD
Paula Pennanen, MSci
Elina Uusitalo, MSci

Clinical Consultants & Collaborators at the University of Turku:
Dermatology: Sirkku Peltonen, MD, PhD
Clinical Genetics: Marja Hietala, MD, PhD
Ophtalmology: Vesa Aaltonen, MD, PhD
Oncology: Eetu Heervä, MD, PhD
Oral Diseases: Vivian Visnapuu, D.Odont., PhD
Pulmonary Diseases: Heli Ylä-Outinen, MD, PhD

Post-doctoral Fellows:
Eetu Heervä, MD, PhD, leave of absence, Part time researcher of the NF-consortium of Turku
 Eeva-Mari Jouhilahti, PhD, leave of absence, Part time researcher of the NF-consortium of Turku

Selected Publications

Uusitalo E, Kallionpää RA, Kurki S, Rantanen M, Pitkäniemi J, Kronqvist P, Härkönen P, Huovinen R, Carpen O, Pöyhönen M, Peltonen S and Peltonen J:  Breast Cancer in Neurofibromatosis Type 1 (NF1): Overrepresentation of Unfavorable Prognostic Factors . Br J Cancer (in press Nov 11, 2016; DOI:10.1038/bjc.2016.403)

Uusitalo E, Rantanen M, Kallionpää RA, Pöyhönen M, Leppävirta J, Ylä-Outinen H, Riccardi VM, Pukkala E, Pitkäniemi J, Peltonen S, and Peltonen J. Distinctive cancer associations in patents with Neurofibromatosis 1. J Clin Oncol 34:1978-1986, 2016

Kangas S, Ohlmeier S, Sormunen R, Jouhilahti E-M, Peltonen S, Peltonen J, Heape A: An approach to comprehensive genome and proteome expression analyses in Schwann cells and neurons during peripheral nerve myelin formation. J Neurochem 138, 830– 844, 2016

Peltonen S, Kallionpää RA, and Peltonen J: Neurofibromatosis type 1 (NF1) gene: Beyond café au lait spots and dermal neurofibromas. Exp Dermatol 2016 Sep 13. doi: 10.1111/exd.13212. [Epub ahead of print]

Uusitalo E, Leppävirta J, Koffert A, Suominen S, Vahtera J, Vahlberg T, Pöyhönen M, Peltonen J and Peltonen S. Incidence and mortality of neurofibromatosis. A total population study in Finland. J Invest Dermatol 135:904-906, 2015

Uusitalo E, Hammais A, Palonen E, Brandt A, Mäkelä V-V, Jouhilahti E-M, Pöyhönen M, Soini J, Pelto-nen J and Peltonen S: Neurofibromatosis type 1 gene mutation analysis using sequence capture and high-throughput sequencing. Acta Derm Venereol 94:663-666, 2014

Heervä E, Koffert A, Jokinen E, Kuorilehto T, Peltonen S, Aro HT and Peltonen J: A controlled register based study of 460 neurofibromatosis 1 (NF1) patients: Increased fracture risk in children and adults over 41 years. J Bone Miner Res 27:2333-2337, 2012

Jouhilahti E-M, Peltonen S, Heape A, Peltonen J: Pathoetiology of neurofibromatosis. Am J Pathol 178:1932-1939, 2011

Heervä E, Alanne MH, Peltonen S, Kuorilehto T, Hentunen T, Väänänen K, and Peltonen J: Osteoclasts in neurofibromatosis type 1 display enhanced resorption capacity, aberrant morphology, and resistance to serum deprivation. Bone 47:583-590, 2010