scholarly journals Functional genomics identifies AMPD2 as a new prognostic marker for undifferentiated pleomorphic sarcoma

2018 ◽  
Vol 144 (4) ◽  
pp. 859-867 ◽  
Author(s):  
Martin F. Orth ◽  
Julia S. Gerke ◽  
Thomas Knösel ◽  
Annelore Altendorf-Hofmann ◽  
Julian Musa ◽  
...  
2018 ◽  
Author(s):  
Martin F. Orth ◽  
Julia S. Gerke ◽  
Thomas Knösel ◽  
Annelore Altendorf-Hofmann ◽  
Julian Musa ◽  
...  

ABSTRACTSoft-tissue sarcomas are rare, heterogeneous and often aggressive mesenchymal cancers. Many of them are associated with poor outcome, in part because biomarkers that can reliably identify high-risk patients are lacking. Studies on sarcomas often are limited by small sample sizes rendering the identification of novel biomarkers difficult when focusing only on individual cohorts. However, the increasing number of publicly available ‘omics’ data opens inroads to overcome this obstacle.Here, we combine high-throughput transcriptome analyses, immunohistochemistry, and functional assays to show that high adenosine monophosphate deaminase 2 (AMPD2) is a robust prognostic biomarker for worse patient outcome in undifferentiated pleomorphic sarcoma (UPS). Publicly available gene expression and survival data for UPS from two independent studies, The Cancer Genome Atlas (TCGA) and the CINSARC reference dataset, were subjected to survival association testing. Genes, whose high expression was significantly correlated with worse outcome in both cohorts (overall and metastasis-free survival), were considered as prognostic marker candidates. The best candidate, AMPD2, was validated on protein level in an independent tissue microarray. Analysis of DNA copy-number and matched gene expression data indicated that high AMPD2 expression is significantly correlated with copy-number gains at the AMPD2 locus. Gene-set enrichment analyses of AMPD2 co-expressed genes in both UPS gene expression datasets suggested that highly AMPD2 expressing tumors are enriched in gene signatures involved in tumorigenesis. Consistent with this prediction in primary tumors, knockdown of AMPD2 by RNA interference with pooled siRNAs or a doxycycline-inducible shRNA construct in the UPS cell line FPS-1 markedly inhibited proliferation in vitro and tumorigenicity in vivo.Collectively, these results provide evidence that AMPD2 may serve as a novel biomarker for outcome prediction in UPS. Our study exemplifies how the integration of available ‘omics’ data, immunohistochemical analyses, and functional experiments can identify novel biomarkers even in a rare sarcoma, which may serve as a blueprint for biomarker identification for other rare cancers.


2017 ◽  
Vol 4 (2) ◽  
pp. 102-104
Author(s):  
Sunil Vitthalrao Jagtap ◽  
◽  
Cyrus Dara Jokhi ◽  
Swati S Jagtap ◽  
Ritvij Patankar ◽  
...  

Rare Tumors ◽  
2021 ◽  
Vol 13 ◽  
pp. 203636132110264
Author(s):  
Andrea Dekanić ◽  
Marko Velepič ◽  
Margita Belušić Gobić ◽  
Ita Hadžisejdić ◽  
Nives Jonjić

Malignant mesenchymal tumors of oropharyngeal mucosa are rare. Those with fibroblastic and histiocytic differentiation in the skin are called atypical fibroxanthoma (AFX) and in the soft tissue undifferentiated pleomorphic sarcoma (UPS). Here we present a case of an older patient with a history of multiple basal cell carcinomas and recently with a rapidly growing polypoid lesion in the mucosa of posterior oropharyngeal wall with AFX/UPS morphology. The differential diagnosis, histological pitfalls of this poorly characterized mesenchymal lesions, and the challenges associated with treatment are discussed.


2020 ◽  
Vol 18 (3) ◽  
Author(s):  
Amita Naithani ◽  
Parul Sharma ◽  
R. Pratima ◽  
Priyanka Makkar ◽  
Sunil Pasricha ◽  
...  

1970 ◽  
Vol 1 (2) ◽  
pp. 151-153 ◽  
Author(s):  
BM Amatya ◽  
M Sawabe ◽  
T Arai ◽  
T Kumakawa ◽  
K Takubo ◽  
...  

(The order of authors on this article was changed on 09/01/2012.)Primary undifferentiated pleomorphic sarcoma of the spleen is a rare and highly aggressive neoplasm that usually presents with splenomegaly, constitutional symptoms and frequent distant metastases. We report a case of 77-year old male patient with a past history of dissecting aortic aneurysm that developed acute hemorrhagic shock. Aneurysmal rupture was clinically suspected, but the postmortem examination revealed a 25 mm-sized tumor in an atrophic spleen weighing 65 gram with massive retroperitoneal bleeding. Metastases were found in the right renal hilus, the right adrenal gland and femoral bone marrow. Histology of the tumor showed undifferentiated pleomorphic sarcoma. Tumor rupture with fatal bleeding and systemic metastases had occurred despite the small size of the tumor. Tumor size is not a reliable predictor of systemic metastasis or tumor rupture for splenic undifferentiated pleomorphic sarcoma. Keywords: Undifferentiated pleomorphic sarcoma; Malignant fibrous histiocytoma; Splenic neoplasms; Retroperitoneal hemorrhage DOI: http://dx.doi.org/10.3126/jpn.v1i2.5411 JPN 2011; 1(2): 151-153


2007 ◽  
Vol 48 (1) ◽  
pp. 131 ◽  
Author(s):  
Sung-Hwan Suh ◽  
Tae-Ho Park ◽  
Jung-Nam Yoo ◽  
Kwang-Soo Cha ◽  
Moo-Hyun Kim ◽  
...  

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