Journal article
High-Resolution Array CGH and Gene Expression Profiling of Alveolar Soft Part Sarcoma
Clinical cancer research, Vol.20(6), pp.1521-1530
03/15/2014
DOI: 10.1158/1078-0432.CCR-13-2090
PMCID: PMC3962657
PMID: 24493828
Abstract
Purpose: Alveolar soft part sarcoma (ASPS) is a soft tissue sarcoma with poor prognosis, and little molecular evidence exists for its origin, initiation, and progression. The aim of this study was to elucidate candidate molecular pathways involved in tumor pathogenesis.
Experimental Design: We employed high-throughput array comparative genomic hybridization (aCGH) and cDNA-Mediated Annealing, Selection, Ligation, and Extension Assay to profile the genomic and expression signatures of primary and metastatic ASPS from 17 tumors derived from 11 patients. We used an integrative bioinformatics approach to elucidate the molecular pathways associated with ASPS progression. FISH was performed to validate the presence of the t(X;17)(p11.2;q25) ASPL-TFE3 fusion and, hence, confirm the aCGH observations.
Results: FISH analysis identified the ASPL-TFE3 fusion in all cases. aCGH revealed a higher number of numerical aberrations in metastatic tumors relative to primaries, but failed to identify consistent alterations in either group. Gene expression analysis highlighted 1,063 genes that were differentially expressed between the two groups. Gene set enrichment analysis identified 16 enriched gene sets (P < 0.1) associated with differentially expressed genes. Notable among these were several stem cell gene expression signatures and pathways related to differentiation. In particular, the paired box transcription factor PAX6 was upregulated in the primary tumors, along with several genes whose mouse orthologs have previously been implicated in Pax6 DNA binding during neural stem cell differentiation.
Conclusion: In addition to suggesting a tentative neural line of differentiation for ASPS, these results implicate transcriptional deregulation from fusion genes in the pathogenesis of ASPS. (C)2014 AACR.
Details
- Title: Subtitle
- High-Resolution Array CGH and Gene Expression Profiling of Alveolar Soft Part Sarcoma
- Creators
- Shamini Selvarajah - Brigham and Women's HospitalSaumyadipta Pyne - Brigham and Women's HospitalEleanor Chen - Brigham and Women's HospitalRamakrishna Sompallae - University of IowaAzra H. Ligon - Brigham and Women's HospitalGunnlaugur P. Nielsen - Brigham and Women's HospitalGlenn Dranoff - Brigham and Women's HospitalEdward Stack - Brigham and Women's HospitalMassimo Loda - Brigham and Women's HospitalRichard Flavin - Brigham and Women's Hospital
- Resource Type
- Journal article
- Publication Details
- Clinical cancer research, Vol.20(6), pp.1521-1530
- DOI
- 10.1158/1078-0432.CCR-13-2090
- PMID
- 24493828
- PMCID
- PMC3962657
- NLM abbreviation
- Clin Cancer Res
- ISSN
- 1078-0432
- eISSN
- 1557-3265
- Publisher
- Amer Assoc Cancer Research
- Number of pages
- 10
- Grant note
- iCureASPS P50CA090381; P01CA089021; R01CA131945 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) RO1CA131945; PO1CA89021; P50 CA90381 / National Cancer Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 03/15/2014
- Academic Unit
- Pathology
- Record Identifier
- 9984622051002771
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