Metastatic potential is determined early in synovial sarcoma development and reflected by tumor molecular features.
BACKGROUND
Synovial sarcoma (SynSa) is an aggressive mesenchymal tumor, comprising approximately 10% of all soft tissue sarcomas. Over half of SynSa patients develop metastasis or local recurrence, but the underlying molecular mechanisms of the aggressive clinical behavior remain poorly characterized.


METHODS
Sixty-four frozen tumor specimens from 54 SynSa patients were subjected to array comparative genomic hybridization (aCGH) and gene expression profiling. The examined set of tumor specimens included 16 primary tumors from untreated patients who did not develop metastasis/local recurrence (SynSa1 group), 26 primary tumors from untreated patients who developed metastases or local recurrence during follow-up (SynSa2 group), and 22 metachronous metastatic/recurrent SynSa tumors (SynSa3 group).


RESULTS
AURKA and KIF18A, which play important roles in various mitotic events, were the two most up-regulated genes in SynSa2 and SynSa3 groups compared to the SynSa1 group. Expression profiles of SynSa2 and SynSa3 tumors did not show any significant differences. Analysis of genomic index (GI) based on aCGH profiles demonstrated that the SynSa1 group consisted of tumors with significantly less complex genomes compared to SynSa2 and SynSa3 groups. There was no significant difference in genome complexity between SynSa2 and SynSa3 tumors.


CONCLUSIONS
Primary SynSa tumors from patients who develop metastases or local recurrence share common molecular features with metastatic/recurrent tumors. Presented data suggest that the aggressive clinical SynSa behavior is determined early in tumorigenesis and might be related to impaired regulation of mitotic mechanisms. This article is part of a Directed Issue entitled: Rare Cancers.
Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland; Department of Human Genetics, KU Leuven and University Hospitals Leuven, Leuven, Belgium; Postgraduate School of Molecular Medicine, Warsaw Medical University, Warsaw, Poland.
Joanna
J
Przybyl
Department of Pathology, KU Leuven and University Hospitals Leuven, Leuven, Belgium.
Raf
R
Sciot
Laboratory of Experimental Oncology, Department of Oncology, KU Leuven, and Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium.
Agnieszka
A
Wozniak
Laboratory of Experimental Oncology, Department of Oncology, KU Leuven, and Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium.
Patrick
P
Schöffski
Department of Human Genetics, KU Leuven and University Hospitals Leuven, Leuven, Belgium.
Vanessa
V
Vanspauwen
Department of Orthopedic Surgery, University Hospitals Leuven, Leuven, Belgium.
Ignace
I
Samson
Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
Janusz A
JA
Siedlecki
Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
Piotr
P
Rutkowski
Department of Human Genetics, KU Leuven and University Hospitals Leuven, Leuven, Belgium. Electronic address: maria.debiec-rychter@med.kuleuven.be.
Maria
M
Debiec-Rychter
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D064096:Aurora Kinase A / Q000096:biosynthesis / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D055028:Comparative Genomic Hybridization; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D059785:Karyotype; D016547:Kinesins / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D057089:Pathology, Molecular; D011379:Prognosis; D012509:Sarcoma / Q000235:genetics* / Q000473:pathology; D013584:Sarcoma, Synovial / Q000235:genetics* / Q000473:pathology
D009363:Neoplasm Proteins; D064096:Aurora Kinase A; C502735:KIF18A protein, human; D016547:Kinesins
Aurora kinase A; Gene expression profiling; Genomic complexity; Kinesin family member 18A; Metastasis; Synovial sarcoma