Fusion of the genes <i>BRD8</i> and <i>PHF1</i> in endometrial stromal sarcoma

Micci, Francesca; Brunetti, Marta; Cin, Paola Dal; Nucci, Marisa R.; Gorunova, Ludmila; Heim, Sverre; Panagopoulos, Ioannis

doi:10.1002/gcc.22485

Cited by 48 publications

(43 citation statements)

References 28 publications

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“…The first chromosomal rearrangement described in LG‐ESS was involved in chromosomes 7 and 17, leading to a fusion between JAZF1 (7p15) and SUZ12 (17q11.2) 11 . Later, other fusions were described, including rearrangements involving PHF1 and multiple partners, such as JAZF1 (7p15), EPC1 (10p11), 12 MEAF6 (1p34), BRD8 (5q31), EPC2 (2q23), and MBTD1‐EZHIP , associated with der(2)t(X;22)(p11;q13) 13‐15 . Described fusion partners for SUZ12 include MEAF6 16 and EPC1 17 …”

Section: Discussionmentioning

confidence: 99%

A novel MBTD1‐PHF1 gene fusion in endometrial stromal sarcoma: A case report and literature review

Han

Liu

Ricciotti

et al. 2020

Genes Chromosomes & Cancer

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The classification of endometrial stromal sarcoma (ESS) has been refined and aided by the discovery of various recurrent gene translocations. Low-grade ESS (LG-ESS) is most commonly characterized by JAZF1-SUZ12 fusions followed by rearrangements involving PHD finger protein-1 (PHF1) and multiple fusion partners, including JAZF1, EPC1, EPC2, and MEAF6. In the present study, integrating anchored polymerase chain reaction and paired-end next-generation ribonucleic acid sequencing, we identified the presence of a novel malignant brain tumor domain-containing 1 (MBTD1)-PHF1 gene fusion in a case of LG-ESS. MBTD1 belongs to the Polycomb gene group, and its fusion with PHF1 is predicted to mediate tumorigenesis through aberrant transcriptional repression. Histology and immunohistochemical studies demonstrated conventional morphology for LG-ESS and clinical follow-up showed no progression of disease after 6 months. These findings help expand the current knowledge on the spectrum of gene rearrangements in the diagnosis of ESS.

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Section: Discussionmentioning

confidence: 99%

A novel MBTD1‐PHF1 gene fusion in endometrial stromal sarcoma: A case report and literature review

Han

Liu

Ricciotti

et al. 2020

Genes Chromosomes & Cancer

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“…PHF1 was first reported as a neoplasia-associated fusion partner in low-grade endometrial stromal sarcomas in which rearrangements of the chromosomal band 6p21 generated the JAZF1-PHF1 and EPC1-PHF1 fusion genes (27). Furthermore, MEAF6-PHF1, BRD8-PHF1, and EPC2-PHF1 fusions have been reported in low-grade endometrial stromal sarcomas (28)(29)(30)(31). Recurrent rearrangement of the PHF1 gene and the fusion genes EP400-PHF1, EPC1-PHF1, and MEAF6-PHF1 have also been reported in ossifying fibromyxoid tumors (17,18,32) and a JAZF1-PHF1 and an AFF3-PHF1 fusion gene have been reported in an unusual ossifying sarcoma of the heart and a myxofibrosarcoma, respectively (33,34).…”

Section: Discussionmentioning

confidence: 99%

Fusion of the Genes PHF1 and TFE3 in Malignant Chondroid Syringoma

Panagopoulos

Gorunova

Lund‐Iversen

et al. 2019

Cancer Genomics Proteomics

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Background/Aim: Malignant chondroid syringoma is a rare tumor of unknown pathogenesis. Materials and Methods: Genetic analyses were performed on a malignant chondroid syringoma. Results: G-banding analysis of shortterm cultured tumor cells yielded the karyotype 46,Y,t(X;6)(p11;p21)[15]/46,XY[2]. RNA sequencing detected an in-frame fusion of PHF1 from 6p21 with TFE3 from Xp11, verified by RT-PCR and Sanger sequencing. Genomic PCR showed that the PHF1-TFE3 junction was identical to the fusion found by RNA sequencing and RT-PCR. Conclusion: Malignant chondroid syringoma is genetically related to tumors with PHF1 rearrangements such as low-grade endometrial sarcoma and ossifying fibromyxoid tumor, but also with tumors having TFE3 rearrangements such as renal cell carcinoma, alveolar soft part sarcoma, PEComa, and epithelioid hemangioendothelioma. Further investigations on malignant chondroid syringomas are needed in order to determine whether genetic heterogeneity exists among them and the clinical impact of the PHF1-TFE3 fusion. Malignant chondroid syringoma, also known as malignant mixed tumor of the skin, is a very rare tumor with less than 50 cases being described in the relevant literature. It is considered to be the malignant counterpart of benign chondroid syringoma (benign mixed tumor) (1, 2). Malignant chondroid syringomas are twice as common in women as in men and show predilection for the trunk and extremities (1-3). The clinical course is unpredictable (4). Half of the reported cases had local recurrences whereas nodal and distant metastases were observed in 39% and 36% of the cases, respectively. The most common sites for distant metastases are the lungs, bone, and brain (4). Malignant chondroid syringoma is composed of both epithelial and mesenchymal tissue. The epithelial component consists of neoplastic cells with hyperchromatic nuclei and abundant mitotic figures, with occasional areas of necrosis. The mesenchymal component may show myxoid, chondroid, osteoid, adipose or fibrous features enclosing clusters of epithelial cells (1-3). Malignant and benign chondroid syringomas are cutaneous myoepithelial neoplasms (5-9). Genetic studies of both cutaneous and soft tissue myoepithelial neoplasms have demonstrated considerable genetic heterogeneity (10-14). In some of these tumors, EWSR1-ZNF444, EWSR1-PBX1, EWSR1-PBX3 or EWSR1-POU5F1 fusion genes have been found (10, 12, 13, 15) whereas others had rearrangements of PLAG1 (11, 14). The differential diagnosis for myoepithelial tumor is extremely broad and may include ossifying fibromyxoid tumors (7, 16). In the latter, the PHD finger protein 1 gene (PHF1) is recurrently rearranged (17) with an EP400-PHF1 fusion being detected in some tumors (17, 18). Herein, we present a malignant chondroid syringoma which had a t(X;6)(p11;p21) as the sole karyotypic aberration. Using RNA sequencing and molecular methodologies, we demonstrated that the molecular consequence of the translocation was the fusion of the PHF1 gene from 6p21 with the transcription factor binding t...

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“…Micci et al show that the PHD finger protein 1 ( PHF1 ) gene from chromosomal band 6p21 recombined with JAZF1 as the partner gene of the JAZF1 gene in LG‐ESS. Further studies have shown that the PHF1 gene from chromosomal band 6p21 recombined with JAZF1 , EPC1 , MEAF6 or BRD8 , which encode the proteins involved in regulation of protein acetylation and/or histone acetyltransferase activity . All these fusions in ESS combined genes are involved in transcriptional regulation; that is, polycomb group complex‐mediated aberration methylation/acetylation; hence, their presumed oncogenic effects may be involved in the pathogenesis of ESS …”

Section: Endometrial Stromal Sarcomamentioning

confidence: 99%

“…Further studies have shown that the PHF1 gene from chromosomal band 6p21 recombined with JAZF1, EPC1, MEAF6 or BRD8, which encode the proteins involved in regulation of protein acetylation and/or histone acetyltransferase activity. 53 All these fusions in ESS combined genes are involved in transcriptional regulation; that is, polycomb group complex-mediated aberration methylation/acetylation; hence, their presumed oncogenic effects may be involved in the pathogenesis of ESS. 52 Currently, ESS is considered to be a tumor with molecular genetic heterogeneity in gene rearrangement.…”

Section: Molecular Biomarker Candidates For Diagnosis and Prognosismentioning

confidence: 99%

Molecular biomarkers for uterine leiomyosarcoma and endometrial stromal sarcoma

Tsuyoshi

Yoshida

2018

Cancer Science

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Uterine leiomyosarcoma (u‐LMS) and endometrial stromal sarcoma (ESS) are among the most frequent soft tissue sarcomas, which, in adults, lead to fatal lung metastases and patients have an extremely poor prognosis. Due to their rarity and heterogeneity, there are no suitable biomarkers for diagnosis and prognosis, although some biomarker candidates have appeared. In 2017, The Cancer Genome Atlas (TCGA) Research Network's work on u‐LMS has confirmed mutations and deletions in RB1,TP53 and PTEN. In addition, whole‐exome sequencing of u‐LMS has confirmed and demonstrated frequent alterations in TP53,RB1, α‐thalassemia/mental retardation syndrome X‐linked (ATRX) and mediator complex subunit 12 (MED12). MED12 is a useful biomarker to diagnose uterine‐derived LMS and tumors arising from (LM) with a relatively favorable prognosis. TP53 and ATRX mutations can be important mechanisms in the pathogenesis of u‐LMS and are correlated with a poor prognosis. In an update based on the 2014 WHO classification, low‐grade ESS is often associated with gene rearrangement bringing about the JAZF 1‐SUZ12 (formerly JAZF1‐JJAZ1) fusion gene, whereas high‐grade ESS is associated with the YWHAE‐NUTM fusion gene. Low‐grade ESS with JAZF1 rearrangement may correlate with metastasis. However, high‐grade ESS with metastasis with YWHAE rearrangement shows a relatively favorable prognosis. The genetic/molecular genetic aberrations in u‐LMS and ESS are reviewed, focusing on molecular biomarkers for these primary and metastatic tumors.

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Fusion of the genes BRD8 and PHF1 in endometrial stromal sarcoma

Cited by 48 publications

References 28 publications

A novel MBTD1‐PHF1 gene fusion in endometrial stromal sarcoma: A case report and literature review

A novel MBTD1‐PHF1 gene fusion in endometrial stromal sarcoma: A case report and literature review

Fusion of the Genes PHF1 and TFE3 in Malignant Chondroid Syringoma

Molecular biomarkers for uterine leiomyosarcoma and endometrial stromal sarcoma

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