Epigenetic regulation of <i>SMARCB1</i> By miR‐206, ‐381 and ‐671‐5p is evident in a variety of SMARCB1 immunonegative soft tissue sarcomas, while miR‐765 appears specific for epithelioid sarcoma. A miRNA study of 223 soft tissue sarcomas

Szepes, Zoltán; Papp, G; Szabó, Miklós; Pápai, Zsuzsanna; Plótár, Vanda; Krausz, Thomas; Fletcher, Christopher D.�M.

doi:10.1002/gcc.22379

Cited by 52 publications

(28 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The study by Hasselblatt et al showed that SMARCB1 deletions were identified in 4/7 (57%) PDC cases by FISH, but only in 2/7 (29%) cases by multiplex ligation‐dependent probe amplification (MLPA), suggesting that FISH is a more sensitive method than MLPA in the context of large homozygous deletions of PDC. In addition, the study by Sápi et al showed that the FISH method detected the presence of deletions in 95% of epithelioid sarcoma cases, while MLPA only in 73% of cases. These findings further confirm our prior results showing high sensitivity of FISH studies to detect homozygous deletions in epithelioid sarcomas compared to MLPA .…”

Section: Discussionmentioning

confidence: 99%

“…In this regard, a recent study found upregulation of miR-671-5p and miR-193a-5p in PDC with loss of SMARCB1 expression. 21 Prior studies on epithelioid sarcomas have also identified epigenetic silencing of SMARCB1 by functionally active miRNAs (miR-206, miR-381 and miR-671-5), 22,23 suggesting an alternative mechanism for loss of SMARCB1 expression in cases lacking genetic evidence of SMARCB1 abnormalities.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

High sensitivity of FISH analysis in detecting homozygous SMARCB1 deletions in poorly differentiated chordoma: a clinicopathologic and molecular study of nine cases

Owosho

Zhang

Rosenblum

et al. 2017

Genes Chromosomes & Cancer

View full text Add to dashboard Cite

Poorly differentiated chordomas (PDCs) represent a rare subset of notochordal neoplasms, affecting primarily children and associated with an aggressive outcome. In contrast to conventional chordomas, PDC show solid growth and increased cellularity, cytologic atypia, and mitotic activity. Recent studies have shown that PDCs are characterized by recurrent deletions encompassing the SMARCB1 locus, resulting in consistent loss of nuclear SMARCB1 expression. Thus PDC joined the expanding family of SMARCB1-deficient tumors characterized by various SMARCB1 structural abnormalities, ranging from large homozygous deletions to small intragenic mutations. In the present study, we investigate the SMARCB1 abnormalities in a group of nine well-characterized PDCs and to establish the sensitivity of the FISH method in detecting these changes in the clinical setting. We further assessed the pathologic features and clinical behavior of this cohort managed at our referral center over a 20-year period. The mean age at diagnosis was 10 years-of-age. All except one case occurred in the cranial region. All demonstrated strong nuclear expression of brachyury and loss of SMARCB1 expression. FISH identified homozygous SMARCB1 deletions in all except one case; additionally two cases revealed a heterozygous EWSR1 locus co-deletion. Clinical follow-up information was available in five patients. Two patients presented with distant metastases at initial diagnosis. Two of the three remaining patients with primary disease failed both locally and distantly after multimodality therapy. We conclude that PDCs are highly aggressive tumors and the dominant mechanism of loss of SMARCB1 expression is through large, homozygous SMARCB1 deletions that can be readily detected by FISH.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

High sensitivity of FISH analysis in detecting homozygous SMARCB1 deletions in poorly differentiated chordoma: a clinicopathologic and molecular study of nine cases

Owosho

Zhang

Rosenblum

et al. 2017

Genes Chromosomes & Cancer

View full text Add to dashboard Cite

show abstract

“…Alterations in SMARCB1 are involved in several cancer types, implicating this event as a driver of these malignancies. 12 This results in a global alteration in chromatin remodeling that needs to be better understood to design targeted therapies.…”

Section: Discussionmentioning

confidence: 99%

Primary renal synovial sarcoma – a diagnostic dilemma

Yellala¹

2018

JCSO

View full text Add to dashboard Cite

FIGURE 1 Coronal section of a computed-tomographic scan of the abdomen and pelvis, showing large right retroperitoneal hematoma with indwelling punctate calcifications, raising concern for underlying retroperitoneal or renal neoplasia and mass. Right kidney is displaced antero-inferiorly. FIGURE 2 Cross-section of the abdomen and pelvis with contrast, showing the liver displaced to the left (1) and the inferior vena cava displaced anteriorly and to the left (2).

show abstract

“…Kohashi et al [15] and Sapi et al [17] both used miRNA expression profiling to distinguish ES from other SD-NRT; both studies identified different but not fully convergent patterns of miRNA expression in ES and RT. Although these studies shed some light on new mechanisms for SMARCB1 down-regulation, they did not inform on the biological origin of the tumors.…”

Section: Discussionmentioning

confidence: 99%

Embryonic signature distinguishes pediatric and adult rhabdoid tumors from other SMARCB1-deficient cancers

et al. 2017

View full text Add to dashboard Cite

Extra-cranial rhabdoid tumors (RT) are highly aggressive malignancies of infancy, characterized by undifferentiated histological features and loss of SMARCB1 expression. The diagnosis is all the more challenging that other poorly differentiated cancers lose SMARCB1 expression, such as epithelioid sarcomas (ES), renal medullary carcinomas (RMC) or undifferentiated chordomas (UC). Moreover, late cases occurring in adults are now increasingly reported, raising the question of differential diagnoses and emphasizing nosological issues. To address this issue, we have analyzed the expression profiles of a training set of 32 SMARCB1-deficient tumors (SDT), with ascertained diagnosis of RT (n = 16, all < 5 years of age), ES (n = 8, all > 10 years of age), UC (n = 3) and RMC (n = 5). As compared with other SDT, RT are characterized by an embryonic signature, and up-regulation of key-actors of de novo DNA methylation processes. Using this signature, we then analysed the expression profiling of 37 SDT to infer the appropriate diagnosis. Thirteen adult onset tumors showed strong similarity with pediatric RT, in spite of older age; by exome sequencing, these tumors also showed genomic features indistinguishable from pediatric RT. In contrary, 8 tumors were reclassified within carcinoma, ES or UC categories, while the remaining could not be related to any of those entities. Our results demonstrate that embryonic signature is shared by all RT, whatever the age at diagnosis; they also illustrate that many adult-onset SDT of ambiguous histological diagnosis are clearly different from RT. Finally, our study paves the way for the routine use of expression-based signatures to give accurate diagnosis of SDT.

show abstract

Epigenetic regulation of SMARCB1 By miR‐206, ‐381 and ‐671‐5p is evident in a variety of SMARCB1 immunonegative soft tissue sarcomas, while miR‐765 appears specific for epithelioid sarcoma. A miRNA study of 223 soft tissue sarcomas

Cited by 52 publications

References 41 publications

High sensitivity of FISH analysis in detecting homozygous SMARCB1 deletions in poorly differentiated chordoma: a clinicopathologic and molecular study of nine cases

High sensitivity of FISH analysis in detecting homozygous SMARCB1 deletions in poorly differentiated chordoma: a clinicopathologic and molecular study of nine cases

Primary renal synovial sarcoma – a diagnostic dilemma

Embryonic signature distinguishes pediatric and adult rhabdoid tumors from other SMARCB1-deficient cancers

Contact Info

Product

Resources

About