Genome wide methylation profiling of selected matched soft tissue sarcomas identifies methylation changes in metastatic and recurrent disease

Vargas, Ana Cristina; Gray, Lesley; White, Christine L.; Maclean, Fiona; Grimison, Peter; Ardakani, Nima Mesbah; Bonar, Fiona; Algar, Elizabeth; Cheah, Alison L.; Russell, Peter; Mahar, Annabelle; Gill, Anthony J.

doi:10.1038/s41598-020-79648-6

Cited by 11 publications

(10 citation statements)

References 76 publications

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“…The reduced level of Ventx in CLL cells promoted Wnt/β-cat and LEF/TCFs interaction, and in turn, induced cyclin D1 expression, leading to cell proliferation and cancer progression. Recently, it was reported that the differential methylation level of Ventx was significantly implicated in sarcoma progression in humans [ 114 ]. A genome-wide methylation-profiling study in metastatic and recurrent sarcomas showed that Ventx was hypermethylated in metastasis pleomorphic rhabdomyosarcoma (Ple-RMS, a rare, aggressive sarcoma with poor prognosis), as compared to primary Ple-RMS.…”

Section: Human Ventx (Vent-like Homeobox Protein 2)mentioning

confidence: 99%

Ventx Family and Its Functional Similarities with Nanog: Involvement in Embryonic Development and Cancer Progression

Kumar

Kim

2022

IJMS

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The Ventx family is one of the subfamilies of the ANTP (antennapedia) superfamily and belongs to the NK-like (NKL) subclass. Ventx is a homeobox transcription factor and has a DNA-interacting domain that is evolutionarily conserved throughout vertebrates. It has been extensively studied in Xenopus, zebrafish, and humans. The Ventx family contains transcriptional repressors widely involved in embryonic development and tumorigenesis in vertebrates. Several studies have documented that the Ventx family inhibited dorsal mesodermal formation, neural induction, and head formation in Xenopus and zebrafish. Moreover, Ventx2.2 showed functional similarities to Nanog and Barx1, leading to pluripotency and neural-crest migration in vertebrates. Among them, Ventx protein is an orthologue of the Ventx family in humans. Studies have demonstrated that human Ventx was strongly associated with myeloid-cell differentiation and acute myeloid leukemia. The therapeutic potential of Ventx family inhibition in combating cancer progression in humans is discussed. Additionally, we briefly discuss genome evolution, gene duplication, pseudo-allotetraploidy, and the homeobox family in Xenopus.

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Section: Human Ventx (Vent-like Homeobox Protein 2)mentioning

confidence: 99%

Ventx Family and Its Functional Similarities with Nanog: Involvement in Embryonic Development and Cancer Progression

Kumar

Kim

2022

IJMS

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“…Deregulation of this epigenetic mechanism has major implications for cancer development and progression ( Diaz-Lagares et al, 2016 ). In this context, recent genome-wide analyses have revealed striking alterations in the methylation profile of uterine uADC and uLMS ( Zhang et al, 2014 ; Kommoss et al, 2020 ; Vargas et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Characterizing the Invasive Tumor Front of Aggressive Uterine Adenocarcinoma and Leiomyosarcoma

Sanegre

Eritja

Andrea

et al. 2021

Front. Cell Dev. Biol.

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The invasive tumor front (the tumor–host interface) is vitally important in malignant cell progression and metastasis. Tumor cell interactions with resident and infiltrating host cells and with the surrounding extracellular matrix and secreted factors ultimately determine the fate of the tumor. Herein we focus on the invasive tumor front, making an in-depth characterization of reticular fiber scaffolding, infiltrating immune cells, gene expression, and epigenetic profiles of classified aggressive primary uterine adenocarcinomas (24 patients) and leiomyosarcomas (11 patients). Sections of formalin-fixed samples before and after microdissection were scanned and studied. Reticular fiber architecture and immune cell infiltration were analyzed by automatized algorithms in colocalized regions of interest. Despite morphometric resemblance between reticular fibers and high presence of macrophages, we found some variance in other immune cell populations and distinctive gene expression and cell adhesion-related methylation signatures. Although no evident overall differences in immune response were detected at the gene expression and methylation level, impaired antimicrobial humoral response might be involved in uterine leiomyosarcoma spread. Similarities found at the invasive tumor front of uterine adenocarcinomas and leiomyosarcomas could facilitate the use of common biomarkers and therapies. Furthermore, molecular and architectural characterization of the invasive front of uterine malignancies may provide additional prognostic information beyond established prognostic factors.

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“…In this study, low level of CNV (copy gain/loss) in MFS was reported as well as methylation alterations in several genes ( MEST , C14MC , FAM136A , SNRPG , CCND2 , TBX15 , PLEC1 , CDH15 ), data which are in accordance with Ogura’s study. 22 , 40 Importance of methylation studies has been mentioned also in the only study available to date using WES and SNP arrays to investigate 20 sarcomas including five MFS, which showed a gradual increase of both nucleotide- and chromosome-level mutations. In particular, they reported that MFS has complex copy number changes but few significant single nucleotide variants.…”

Section: Diagnosis and Prognosismentioning

confidence: 99%

Myxofibrosarcoma landscape: diagnostic pitfalls, clinical management and future perspectives

et al. 2022

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Myxofibrosarcoma (MFS) is a common entity of adult soft tissue sarcomas (STS) characterized by a predilection of the extremities and a high local recurrence rate. Originally classified as a myxoid variant of malignant fibrous histiocytoma, this musculoskeletal tumor has been recognized since 2002 as a distinct histotype showing a spectrum of malignant fibroblastic lesions with myxoid stroma, pleomorphism and curvilinear vessels. Currently, the molecular pathogenesis of MFS is still poorly understood and its genomic profile exhibits a complex karyotype with a number of aberrations including amplifications, deletions and loss of function. The diagnosis is challenging due to the unavailability of specific immunohistochemical markers and is based on the analysis of cytomorphologic features. The mainstay of treatment for localized disease is represented by surgical resection, with (neo)-adjuvant radio- and chemotherapy. In the metastatic setting, chemotherapy represents the backbone of treatments, however its role is still controversial and the outcome is very poor. Recent advent of genomic profiling, targeted therapies and larger enrollment of patients in translational and clinical studies, have improved the understanding of biological behavior and clinical outcome of such a disease. This review will provide an overview of current diagnostic pitfalls and clinical management of MFS. Finally, a look at future directions will be discussed.

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Genome wide methylation profiling of selected matched soft tissue sarcomas identifies methylation changes in metastatic and recurrent disease

Cited by 11 publications

References 76 publications

Ventx Family and Its Functional Similarities with Nanog: Involvement in Embryonic Development and Cancer Progression

Ventx Family and Its Functional Similarities with Nanog: Involvement in Embryonic Development and Cancer Progression

Characterizing the Invasive Tumor Front of Aggressive Uterine Adenocarcinoma and Leiomyosarcoma

Myxofibrosarcoma landscape: diagnostic pitfalls, clinical management and future perspectives

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