Identification of Novel Fusion Transcripts in Undifferentiated Pleomorphic Sarcomas by Transcriptome Sequencing

Zheng, Biqiang; Zhang, Shuirong; Cai, Weiluo; Wang, Jian; Wang, Ting; Shi, Yingqiang; Luo, Xiaoying; Yan, Wangjun

doi:10.21873/cgp.20144

Cited by 3 publications

(4 citation statements)

References 34 publications

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“…This research helped us to understand the molecular characteristics of UPS more deeply, and given us a certain understanding of UPS chemotherapy resistance. In addition, some new fusion genes including PDGFRA-MACROD2, NCOR1-MAP2K1 were found in Zheng’s research, which provided an important clue for targeted therapy 31. As for adjuvant radiotherapy, Belal9 reported that adjuvant radiotherapy was related to a decreased risk of local recurrence and Hsu17 showed it could improve local control, while our data showed no benefit in prolong overall survival time, local recurrence time and metastasis time.…”

Section: Discussionmentioning

confidence: 54%

<p>Undifferentiated Pleomorphic Sarcoma: Long-Term Follow-Up from a Large Institution</p>

Chen

Huang

Luo

et al. 2019

CMAR

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PurposeOur study aimed to describe the clinical features of undifferentiated pleomorphic sarcoma (UPS) and identify the predictors of poor outcomes.Patients and methodsThe clinicopathological variables and treatment strategies of 100 UPS patients who underwent surgical resections at a single institution between November 2004 and July 2016 were reviewed. Kaplan–Meier and Cox regression method were conducted for survival analysis.ResultsThe median follow-up time was 94 months (range, 1.5–154 months). R0 resection was applied for 72 cases, and the median tumor size was 5.75cm (range, 1–30cm). Tumor grades of 45 patients were intermediate grade (G2), and 54 patients were with advanced stage (stage III/IV). Twenty-seven patients presented with tumors involving important structures, in which the nerve was the most frequently invaded structure (n=12). During the follow-up, 40 patients suffered from postoperative local recurrence, and distant metastasis was observed in 25 patients which mainly metastasized to the lung (n=14). The 5-year OS rate, 5-year LRFS rate, and 5-year MFS rate was 53%, 55%, and 70%, respectively. Multivariate analysis revealed that tumor presentation, tumor size, and important structures involved (p=0.033, p=0.004, and p=0.033, respectively) were independent prognostic factors associated with OS. Meanwhile, age, resection quality and tumor grade were independent prognostic factors for LRFS (p=0.033, p=0.045, and p=0.007, respectively) and tumor depth was significantly associated with MFS (p=0.050) in multivariate analysis.ConclusionPrimary treatment of UPS should be conducted by experts in large sarcoma center. Wide surgical margin provides sufficient control of the disease recurrence.

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Section: Discussionmentioning

confidence: 54%

<p>Undifferentiated Pleomorphic Sarcoma: Long-Term Follow-Up from a Large Institution</p>

Chen

Huang

Luo

et al. 2019

CMAR

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“…A specific recurring deletion of exon 6 has been observed in esophageal squamous cell carcinoma and gastric cancer [98]. For MACROD1, a RUNX-MACROD1 fusion was identified in leukaemia [99] and, for MACROD2, a PDGFRA-MACROD2 fusion in a pleomorphic sarcoma [100]. Despite the low number of identified mutations in patient tumour samples, several reports have correlated MACROD1 or MACROD2 expression levels with the clinical outcome, as described in the next paragraphs.…”

Section: Mono(adp-ribosyl)ation In Cancermentioning

confidence: 99%

The Controversial Roles of ADP-Ribosyl Hydrolases MACROD1, MACROD2 and TARG1 in Carcinogenesis

Feijs

Cooper

Žaja

2020

Cancers

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Post-translational modifications (PTM) of proteins are crucial for fine-tuning a cell's response to both intracellular and extracellular cues. ADP-ribosylation is a PTM, which occurs in two flavours: modification of a target with multiple ADP-ribose moieties (poly(ADP-ribosyl)ation or PARylation) or with only one unit (MARylation), which are added by the different enzymes of the PARP family (also known as the ARTD family). PARylation has been relatively well-studied, particularly in the DNA damage response. This has resulted in the development of PARP inhibitors such as olaparib, which are increasingly employed in cancer chemotherapeutic approaches. Despite the fact that the majority of PARP enzymes catalyse MARylation, MARylation is not as well understood as PARylation. MARylation is a dynamic process: the enzymes reversing intracellular MARylation of acidic amino acids (MACROD1, MACROD2, and TARG1) were discovered in 2013. Since then, however, little information has been published about their physiological function. MACROD1, MACROD2, and TARG1 have a 'macrodomain' harbouring the catalytic site, but no other domains have been identified. Despite the lack of information regarding their cellular roles, there are a number of studies linking them to cancer. However, some of these publications oppose each other, some rely on poorly-characterised antibodies, or on aberrant localisation of overexpressed rather than native protein. In this review, we critically assess the available literature on a role for the hydrolases in cancer and find that, currently, there is limited evidence for a role for MACROD1, MACROD2, or TARG1 in tumorigenesis.

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“…According to data from the Surveillance, Epidemiology, and End Results (SEER) program, UPS comprises 17.1% of cases of STSs (2). The mainstay of treatment for UPS is surgical resection with adequate margins, with consideration given to perioperative RT and chemotherapy (3,4). UPS is notorious for a high rate of recurrence with high metastatic potential, making the management of UPS difficult, and the prognosis is poor for patients Frontiers in Oncology frontiersin.org 01…”

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confidence: 99%

“…with metastatic or surgically unresectable disease (4). Here, we present a patient with UPS involving the chest wall who received treatment with ICIs prior to the diagnosis of UPS.…”

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confidence: 99%

Case Report: An exceptional response to neoadjuvant radiotherapy and chemotherapy in undifferentiated pleomorphic sarcoma following checkpoint inhibitor use

et al. 2023

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Undifferentiated pleomorphic sarcoma (UPS), a subtype of soft tissue sarcoma (STS), is an uncommon malignancy associated with a poor prognosis. As with other forms of sarcoma, surgical resection remains the only form of treatment with curative potential. The role of perioperative systemic therapy has not been definitively elucidated. Due to high recurrence rates and metastatic potential, management of UPS can pose a difficult task for clinicians. In cases of unresectable UPS due to anatomic limitations and in patients with comorbidities and poor performance status (PS), management options are limited. We describe a patient with UPS involving the chest wall with poor PS who achieved complete response (CR) following neoadjuvant chemotherapy and radiation in the setting of prior immune-checkpoint inhibitor (ICI) therapy.

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Identification of Novel Fusion Transcripts in Undifferentiated Pleomorphic Sarcomas by Transcriptome Sequencing

Cited by 3 publications

References 34 publications

<p>Undifferentiated Pleomorphic Sarcoma: Long-Term Follow-Up from a Large Institution</p>

<p>Undifferentiated Pleomorphic Sarcoma: Long-Term Follow-Up from a Large Institution</p>

The Controversial Roles of ADP-Ribosyl Hydrolases MACROD1, MACROD2 and TARG1 in Carcinogenesis

Case Report: An exceptional response to neoadjuvant radiotherapy and chemotherapy in undifferentiated pleomorphic sarcoma following checkpoint inhibitor use

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