The Genetics of Soft Tissue Tumors

Soft tissue tumors (STT) constitute a heterogeneous group of approximately 100 distinct neoplasms, including more than 50 malignant subtypes, so-called sarcomas. Genetic analyses have shown that the clinical and biological variation among these neoplasms is reflected in their genotypes. While the diagnosis of STT has been improved by such genetic biomarkers, the use of genetic information for improved treatment stratification or for developing new treatment targets lags behind. Apart from identifying and implementing new STT biomarkers in the clinic, we pursue three different lines of investigation, aiming at (1) distiguishing patients with low and high, respectively, risks for relapse; (2) evaluating the cellular effects of driver mutations, such as gene fusions; and (3) understanding the genetic mechanisms causing genetic instability and clonal evolution. These questions will be resolved by combining comprehensive genetic analyses with functional studies and thorough clinical correlations. The identification of specific mutations is of immediate clinical importance by providing improved diagnostic precision and opportunities for prognostic evaluation. Furthermore, the results of our studies will shed light on potential new therapeutic targets.  

For publications: https://orcid.org/0000-0002-6278-5232 or https://scholar.google.se/citations?user=nJU-vUQAAAAJ&hl=sv

5 selected publications:
 

Hofvander J, Jo VY, Fletcher CDM, Puls F, Flucke U, Nilsson J, Magnusson L, Mertens F. PHF1 fusions cause distinct gene expression and chromatin accessibility profiles in ossifying fibromyxoid tumors and mesenchymal cells. Mod Pathol 2020;33:1331-1340.

Puls F, Aigamy A, Flucke U, Menzel T, Sumathi VP, Ploegmakers M, Stoehr R, Kindblom L-G, Hansson M, Sydow S, Arbajian E, Mertens F. Recurrent fusions between YAP1 and KMT2A in morphologically distinct neoplasms within the spectrum of low-grade fibromyxoid sarcoma and sclerosing epithelioid fibrosarcoma. Am J Surg Pathol 2020;44:594-606.

Al-Ibraheemi A, Folpe AL, Perez-Atayde AR, Perry K, Hofvander J, Arbajian E, Magnusson L, Nilsson J, Mertens F. Aberrant receptor tyrosine kinase signaling in lipofibromatosis: a clinicopathological and molecular genetic study of 20 cases. Mod Pathol 2019;32:423-434.

Hofvander J, Viklund B, Isaksson A, Brosjö O, Vult von Steyern F, Rissler P, Mandahl N, Mertens F. Different patterns of clonal evolution among different sarcoma subtypes followed for up to 25 years. Nat Commun 2018;9:3662.

Arbajian E, Puls F, Antonescu CR, Amary F, Sciot R, Debiec-Rychter M, Järås M, Magnusson L, Nilsson J, Hofvander J, Mertens F. In-depth genetic analysis of sclerosing epithelioid fibrosarcoma reveals recurrent genomic alterations and potential treatment targets. Clin Cancer Res 2017;23:7426-7434.