TY - JOUR

T1 - Indistinguishable genomic profiles and shared prognostic markers in undifferentiated pleomorphic sarcoma and leiomyosarcoma: different sides of a single coin?

AU - Carneiro, Ana

AU - Francis, Princy

AU - Bendahl, Pär-Ola

AU - Fernebro, Josefin

AU - Akerman, Måns

AU - Fletcher, Christopher

AU - Rydholm, Anders

AU - Borg, Ake

AU - Nilbert, Mef

N1 - Keywords: Adult; Aged; Aged, 80 and over; Case-Control Studies; Chromosomes, Human; Cluster Analysis; Diagnosis, Differential; Gene Dosage; Gene Expression Profiling; Histiocytoma, Malignant Fibrous; Humans; Leiomyosarcoma; Liposarcoma; Middle Aged; Neoplasm Invasiveness; Oligonucleotide Array Sequence Analysis; Prognosis; Retrospective Studies; Tumor Markers, Biological

PY - 2009

Y1 - 2009

N2 - Soft tissue sarcoma (STS) diagnostics and prognostics are challenging, particularly in highly malignant and pleomorphic subtypes such as undifferentiated pleomorphic sarcoma (UPS) and leiomyosarcoma (LMS). We applied 32K BAC arrays and gene expression profiling to 18 extremity soft tissue LMS and 31 extremity soft tissue UPS with the aim of identifying molecular subtype signatures and genomic prognostic markers. Both the gains/losses and gene expression signatures revealed striking similarities between UPS and LMS, which were indistinguishable using unsupervised hierarchical cluster analysis and significance analysis for microarrays. Gene expression analysis revealed just nine genes, among them tropomyosin beta, which were differentially expressed. Loss of 4q31 (encompassing the SMAD1 locus), loss of 18q22, and tumor necrosis were identified as independent predictors of metastasis in multivariate stepwise Cox regression analysis. Combined analysis applying loss of 4q31 and 18q22 and the presence of necrosis improved the area under receiver operating characteristic curve for metastasis prediction from 0.64 to 0.86. The extensive genetic similarities between extremity soft tissue UPS and LMS suggest a shared lineage of these STS subtypes and the new and independent genetic prognosticators identified hold promise for refined prognostic determination in high-grade, genetically complex STS.

AB - Soft tissue sarcoma (STS) diagnostics and prognostics are challenging, particularly in highly malignant and pleomorphic subtypes such as undifferentiated pleomorphic sarcoma (UPS) and leiomyosarcoma (LMS). We applied 32K BAC arrays and gene expression profiling to 18 extremity soft tissue LMS and 31 extremity soft tissue UPS with the aim of identifying molecular subtype signatures and genomic prognostic markers. Both the gains/losses and gene expression signatures revealed striking similarities between UPS and LMS, which were indistinguishable using unsupervised hierarchical cluster analysis and significance analysis for microarrays. Gene expression analysis revealed just nine genes, among them tropomyosin beta, which were differentially expressed. Loss of 4q31 (encompassing the SMAD1 locus), loss of 18q22, and tumor necrosis were identified as independent predictors of metastasis in multivariate stepwise Cox regression analysis. Combined analysis applying loss of 4q31 and 18q22 and the presence of necrosis improved the area under receiver operating characteristic curve for metastasis prediction from 0.64 to 0.86. The extensive genetic similarities between extremity soft tissue UPS and LMS suggest a shared lineage of these STS subtypes and the new and independent genetic prognosticators identified hold promise for refined prognostic determination in high-grade, genetically complex STS.

U2 - 10.1038/labinvest.2009.18

DO - 10.1038/labinvest.2009.18

M3 - Journal article

C2 - 19290004

VL - 89

SP - 668

EP - 675

JO - Laboratory Investigation

JF - Laboratory Investigation

SN - 0023-6837

IS - 6

ER -