The clinical value of genetic analyses of bone and soft tissue tumors

Sammanfattning: Tumors of bone and soft tissue are common but only constitute 1 % of all malignant tumors. The malignant tumors are often difficult to diagnose due to their rarity and morphological resemblance between subtypes. This makes the diagnostic process challenging. Thus, there is a need for ancillary techniques, such as genetic analyses, not only for diagnostic purposes, but also for obtaining information that could be useful for treatment and prognosis. Different types of bone and soft tissue tumors, both benign and malignant, were analyzed. The tumor material used included needle aspiration biopsies, fresh and frozen surgical biopsies and formalin-fixed tissue. In paper I we compared karyotypes obtained by fine needle aspiration (FNA), core-needle (CNB) and surgical biospies. Chromosome banding analysis found clonal aberrations in 64% of surgical biopsies, in 48% of CNB and in 24% of FNA. These results suggest that chromosome banding analysis should be avoided on FNA and CNB. In paper II a pediatric giant fibroadenoma was analyzed with SNP array, revealing trisomies, uniparental isodisomy for chromosomes 10, 11 and 22 and a homozygous deletion of PARVA, indicating that SNP array provides information on pediatric breast tumors. In paper III we showed that the balanced translocation t(7;19)(q22;q13) results in a novel fusion gene SERPINE1-FOSB, which characterizes a malignant vascular tumor called pseudomyogenic hemangioendothelioma. The results were obtained by combining FISH, PCR and NGS-based RNA sequencing. In paper IV we successfully used RNA sequencing on formalin-fixed tissue to search for gene fusions in benign fibrous histiocytoma; a novel member of the protein kinase C family was shown to be involved. In paper V we studied pediatric rhabdomyosarcomas using mainly SNP array. We could show that this technique reveals many diagnostically and prognostically important aberrations, but that additional technologies for gene fusion detection must be employed. Thus, different genetic techniques provide different types of information, which must be taken into account when selecting method(s) for clinical, diagnostic purposes. None of the techniques used in the present studies is sufficient for detecting all clinically relevant genetic aberrations in bone and soft tissue tumors.