Corrigendum: Next-Generation Sequencing Approaches for the Identification of Pathognomonic Fusion Transcripts in Sarcomas: The Experience of the Italian ACC Sarcoma Working Group.

[This corrects the article DOI: 10.3389/fonc.2020.

Next-Generation Sequencing Approaches for the Identification of Pathognomonic Fusion Transcripts in Sarcomas: The Experience of the Italian ACC Sarcoma Working Group.

This work describes the set-up of a shared platform among the laboratories of the Alleanza Contro il Cancro (ACC) Italian Research Network for the identification of fusion transcripts in sarcomas by using Next Generation Sequencing (NGS). Different NGS approaches, including anchored multiplex PCR and hybrid capture-based panels, were employed to profile a large set of sarcomas of different histotypes. The analysis confirmed the reliability of NGS RNA-based approaches in detecting sarcoma-specific rearrangements.

Primary Vascular Tumors of Bone: A Monoinstitutional Morphologic and Molecular Analysis of 427 Cases With Emphasis on Epithelioid Variants.

Recent molecular discoveries have refined vascular bone tumor classification. To investigate the clinical relevance of these refinements, we reviewed all cases of primary vascular bone tumors treated at our Institute. On the basis of morphology, cases were assessed immunohistochemically and molecularly.

Pazopanib for treatment of advanced extraskeletal myxoid chondrosarcoma: a multicentre, single-arm, phase 2 trial.

Background: Extraskeletal myxoid chondrosarcoma is a rare sarcoma with low sensitivity to cytotoxic chemotherapy. Retrospective evidence suggests that antiangiogenic drugs could be a treatment option. We aimed to investigate the activity of pazopanib, an antiangiogenic drug, in patients with advanced extraskeletal myxoid chondrosarcoma.

NR4A3 fusion proteins trigger an axon guidance switch that marks the difference between EWSR1 and TAF15 translocated extraskeletal myxoid chondrosarcomas.

Extraskeletal myxoid chondrosarcoma (EMC) is a rare sarcoma histotype with uncertain differentiation. EMC is hallmarked by the rearrangement of the NR4A3 gene, which in most cases fuses with EWSR1 or TAF15. TAF15-translocated EMC seem to feature a more aggressive course compared to EWSR1-positive EMCs, but whether the type of NR4A3 chimera impinges upon EMC biology is still largely undefined.

A Pediatric Intra-Axial Malignant SMARCB1-Deficient Desmoplastic Tumor Arising in Meningioangiomatosis.

SMARCB1 inactivation is a well-established trigger event in atypical teratoid/rhabdoid tumor. Recently, a role for SMARCB1 inactivation has emerged as a mechanism of clonal evolution in other tumor types, including rare brain tumors. We describe an unusual malignant intra-axial SMARCB1-deficient spindle cell desmoplastic neoplasm, occurring in a 6-year-old child with meningioangiomatosis and a long history of seizures.

Identification of SRF-E2F1 fusion transcript in EWSR-negative myoepithelioma of the soft tissue.

Myoepithelial neoplasms (MN) are rare and not well-circumstanced entities displaying a heterogeneous spectrum of genetic abnormalities, including EWSR1, FUS and PLAG1 rearrangements. However, in the remaining MN no other fusion gene has been described and knowledge concerning secondary acquired molecular alterations is still poor. Therefore, we screened 5 cases of MN of the soft tissue by RNA sequencing with the aim of identifying novel fusion transcripts.

The co-existence of transcriptional activator and transcriptional repressor MEF2 complexes influences tumor aggressiveness.

The contribution of MEF2 TFs to the tumorigenic process is still mysterious. Here we clarify that MEF2 can support both pro-oncogenic or tumor suppressive activities depending on the interaction with co-activators or co-repressors partners. Through these interactions MEF2 supervise histone modifications associated with gene activation/repression, such as H3K4 methylation and H3K27 acetylation.

Sunitinib-induced morpho-functional changes and drug effectiveness in malignant solitary fibrous tumours.

Sunitinib improves the outcomes of patients with solitary fibrous tumours (SFTs). The aim of this study was to investigate and contextualise sunitinib-induced morpho-functional changes in order to gain insights into the drug's mechanism of action.To this end, four surgical specimens obtained from two sunitinib-responsive patients with malignant SFT, and one primary cell culture obtained from fresh tumoral tissue and its stabilised cell line, were studied by means of immunohistochemistry, bright field in situ hybridisation, immunofluorescence/confocal microscopy, and biochemistry.

Evolution of Dermatofibrosarcoma Protuberans to DFSP-Derived Fibrosarcoma: An Event Marked by Epithelial-Mesenchymal Transition-like Process and 22q Loss.

Unlabelled: Dermatofibrosarcoma protuberans (DFSP) is a rare and indolent cutaneous sarcoma. At times, a fibrosarcomatous transformation marked by a more aggressive clinical behavior may be present. We investigated the natural history and the molecular bases of progression from classic DFSP to the fibrosarcomatous form (FS-DFSP), looking, retrospectively, at the outcome of all patients affected by primary DFSP treated at our institution from 1993 to 2012 and analyzing the molecular profile of 5 DFSPs and 5 FS-DFSPs by an integrated genomics approach (whole transcriptome sequencing, copy number analysis, FISH, qRT-PCR, IHC).

Transcriptome sequencing identifies ETV6-NTRK3 as a gene fusion involved in GIST.

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. The vast majority of GISTs are driven by oncogenic activation of KIT, PDGFRA or, less commonly, BRAF. Loss of succinate dehydrogenase complex activity has been identified in subsets of KIT/PDGFRA/BRAF-mutation negative tumours, yet a significant fraction of GISTs are devoid of any of such alterations.

Massive parallel sequencing in sarcoma pathobiology: state of the art and perspectives.

Sarcomas are an aggressive and highly heterogeneous group of mesenchymal malignancies with different morphologies and clinical behavior. Current therapeutic strategies remain unsatisfactory. Cytogenetic and molecular characterization of these tumors is resulting in the breakdown of the classical histopathological categories into molecular subgroups that better define sarcoma pathobiology and pave the way to more precise diagnostic criteria and novel therapeutic opportunities.

YAP1 acts as oncogenic target of 11q22 amplification in multiple cancer subtypes.

The transcriptional coactivator YAP1 is a critical effector of the human Salvador-Warts-Hippo pathway. Literature data report apparently discrepant results on the carcinogenic role of YAP1, which acts either as oncogene or as tumor suppressor in different in vitro and in vivo models. Furthermore, genomic amplification events of 11q22 locus encompassing YAP1 gene have been detected in multiple tumor types but there is limited direct evidence about the oncogenic role of endogenous YAP1 within in the amplicon.

SMARCB1/INI1 genetic inactivation is responsible for tumorigenic properties of epithelioid sarcoma cell line VAESBJ.

Epithelioid sarcoma is a rare soft tissue neoplasm that usually arises in the distal extremities of young adults. Epithelioid sarcoma presents a high rate of recurrences and metastases and frequently poses diagnostic dilemmas. We previously reported loss of tumor suppressor SMARCB1 protein expression and SMARCB1 gene deletion in the majority of epithelioid sarcoma cases.

Case report: long-term survival of an infant syndromic patient affected by atypical teratoid-rhabdoid tumor.

Background: Atypical teratoid rhabdoid tumor (ATRT) patients display a dismal median overall survival of less than 1 year. A consistent fraction of cases carries de-novo SMARCB1/INI1 constitutional mutations in the setting of the "rhabdoid tumor predisposition syndrome" and the outcome is worst in infant syndromic ATRT patients.

Case Presentation: We here describe a patient affected by mosaic Klinefelter syndrome and by rhabdoid tumor predisposition syndrome caused by constitutional SMARCB1/INI1 heterozygous mutation c.