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Tytuł:
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Chromosome instability accounts for reverse metastatic outcomes of pediatric and adult synovial sarcomas.
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Autorzy:
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Lagarde P; Institut Nationalde la Santé et de la Recherche Médicale (INSERM) U916-Institut Bergonie, France.
Przybyl J
Brulard C
Pérot G
Pierron G
Delattre O
Sciot R
Wozniak A
Schöffski P
Terrier P
Neuville A
Coindre JM
Italiano A
Orbach D
Debiec-Rychter M
Chibon F
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Źródło:
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Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2013 Feb 10; Vol. 31 (5), pp. 608-15. Date of Electronic Publication: 2013 Jan 14.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: 2003- : Alexandria, VA : American Society of Clinical Oncology
Original Publication: New York, N.Y. : Grune & Stratton, c1983-
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MeSH Terms:
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Chromosomal Instability*
Biomarkers, Tumor/*genetics
Carrier Proteins/*genetics
Cell Cycle Proteins/*genetics
Kinesins/*genetics
Nuclear Proteins/*genetics
Oncogene Proteins/*genetics
Sarcoma, Synovial/*genetics
Sarcoma, Synovial/*pathology
Adolescent ; Adult ; Child ; DNA Copy Number Variations ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Kaplan-Meier Estimate ; Male ; Prognosis ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Sarcoma, Synovial/therapy ; Young Adult
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Substance Nomenclature:
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0 (Biomarkers, Tumor)
0 (CDCA2 protein, human)
0 (Carrier Proteins)
0 (Cell Cycle Proteins)
0 (Nuclear Proteins)
0 (Oncogene Proteins)
EC 3.6.1.- (KIF14 protein, human)
EC 3.6.4.4 (Kinesins)
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Entry Date(s):
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Date Created: 20130116 Date Completed: 20130329 Latest Revision: 20220410
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Update Code:
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20240104
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DOI:
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10.1200/JCO.2012.46.0147
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PMID:
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23319690
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Purpose: Synovial sarcoma (SS) occurs in both children and adults, although metastatic events are much more common in adults. Whereas the importance of the t(X;18) translocation in SS oncogenesis is well established, the genetic basis of SS metastasis is still poorly understood. We recently reported expression (CINSARC; Complexity Index in Sarcoma) and Genomic Index prognostic signatures related to chromosome integrity in sarcomas and GI stromal tumors. Here we investigate whether these signatures can also predict outcomes in SS.
Patients and Methods: One hundred patients who had primary untreated SS tumors were selected for expression and genomic profiling in a training/validation approach.
Results: CINSARC and Genomic Index have strong independent and validated prognostic values (P < .001). By comparing expression profiles of tumors with or without metastasis, 14 genes that are common to the CINSARC signature were identified, and the two top-ranked genes, KIF14 and CDCA2, were validated as prognostic markers in an independent cohort. Comparing genomic profiles of adult versus pediatric SS, we show that metastasis is associated with genome complexity in both situations and that the adult genome is more frequently rearranged. Accordingly, pediatric patients with an even genomic profile do not develop metastasis.
Conclusion: Metastasis development in SS is strongly associated with chromosome complexity, and CINSARC and Genomic Index are validated independent prognostic factors. The differences in metastasis frequency between adults and children are associated with genome instability, which is much more frequent in adults. Genomic Index is potentially the best overall biomarker and clearly the most clinically relevant, considering that genome profiling from formalin-fixed samples is already used in pathology.
