Rhabdomyosarcoma in children – current pathologic and molecular classification

Dziuba, Ireneusz; Kurzawa, Paweł; Dopierała, Michał; Larque, Ana B.; Januszkiewicz‐Lewandowska, Danuta

doi:10.5114/pjp.2018.75333

Cited by 56 publications

(73 citation statements)

References 17 publications

(28 reference statements)

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“…New molecular targets being explored include inhibiting tyrosine kinase receptors such as epidermal growth factor receptor (erlotinib, geftinib), platelet derived growth factor receptor (olaratumab, dasatinib, pazotinib, sorafenib), vascular endothelial growth factor receptor (sunitinib, apatinib) and anaplastic lymphoma kinase receptor (crizotinib, ceritinib) [6]. Monoclonal antibodies against insulin-like growth factor 1 receptor (cixutumumab, R1507, BMS-754807) have shown promise in early phases of clinical trials [4,6]. Cyclin-dependent kinase inhibitors (palbociclib), and mouse double minute 2 homolog-tumour -tumour protein p53 interaction inhibitor (MI-63) have shown some promise in phase I clinical trials [6].…”

Section: Resultsmentioning

confidence: 99%

“…Cyclin-dependent kinase inhibitors (palbociclib), and mouse double minute 2 homolog-tumour -tumour protein p53 interaction inhibitor (MI-63) have shown some promise in phase I clinical trials [6]. The role of small GTP-ases family inhibitors (cetuximab, panitumumab, sorafenib), BRAF inhibitors (veumurafenib, dabrafenib) and mitogen activated protein kinase in hibitors (sorafenib, selumetinib, AZD8055) in reducing tumour growth is being explored in preclinical studies [4,7]. Other targets being explored include mammalian target of rapamycin kinase inhibitors (sirolimus, everolimus), phosphadidylinisitol-4,5-bisphosphate 3 kinase inhibitors (temsirolimus, ridaforolimus), programmed cell death-1 receptor inhibitor (pembrolizumab) and polycomb-group locations t(2;13)(q35;q14) or t(1;13) (p36;q14), which lead to the formation of chimeric transcription factors (PAX3-FKHR or PAX7-FKHR, respectively).…”

Section: Resultsmentioning

confidence: 99%

“…Other targets being explored include mammalian target of rapamycin kinase inhibitors (sirolimus, everolimus), phosphadidylinisitol-4,5-bisphosphate 3 kinase inhibitors (temsirolimus, ridaforolimus), programmed cell death-1 receptor inhibitor (pembrolizumab) and polycomb-group locations t(2;13)(q35;q14) or t(1;13) (p36;q14), which lead to the formation of chimeric transcription factors (PAX3-FKHR or PAX7-FKHR, respectively). These transcription factors cause cell proliferation, angiogenesis and other cancerous changes [3,4]. As our patient did not have enough resources, we could not proceed with mutational analysis for genotype-phenotype correlation.…”

Section: Resultsmentioning

confidence: 99%

“…As previously mentioned, the two major histological subtypes of rhabdomyosarcoma are embryonal and alveolar. Our patient had been afflicted by the alveolar subtype as histological examination showed the presence of distinct alveolar architecture with aggregates of small round undifferentiated cells separated by dense hyalinized fibrous septa [3,4]. The alveolar subtype accounts for 15-20% of all cases, typically occurs in the second decade of life, has a higher propensity to metastasise and is usually located in the extremities [5].…”

Section: Discussionmentioning

confidence: 99%

“…rhabdomyosarkom -hýždě -chemoterapie protein inhibitors (tazemetostat) [4,5,8]. Drugs targeting the PAX-FKHR fusion proteins (synthetic retinoid fenretinide, fascaplysin) have been isolated, which need further evaluation [5].…”

Section: Klíčová Slovamentioning

confidence: 99%

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Rhabdomyosarcoma of the Gluteus Maximus – Case Report, Review of Literature and Emerging Therapeutic Targets

Meshram¹,

Kaur²,

Hura³

2019

Klin Onkol

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Background: Rhabdomyosarcoma is an uncommon mesodermal cancer, which predominantly affects the young population. Common sites of primary disease include the head and neck region, genitourinary tract and the extremities. Less than 25% of the cases of rhabdomyosarcoma are metastatic at presentation. Embryonal and alveolar are the most common histological subtypes of rhabdomyosarcoma. Literature about rhabdomyosarcoma located in the gluteal region is sparse. Case: We present a case of a 3-year-old child with alveolar rhabdomyosarcoma arising from the gluteal region. The metastatic workup was negative. We determined the tumour to be of intermediate risk and managed the patient with systemic chemotherapy consisting of cycles of vincristine, actinomycin D and cyclophosphamide, along with local treatment (wide-margin excision and radiotherapy). No recurrence was observed in the follow-up period. Conclusion: Management of alveolar rhabdomyosarcoma of the gluteus maximus requires a multipronged approach consisting of systemic chemotherapy, local surgery and radiotherapy. Long-term surveillance is imperative in children for early identification and management of relapses and treatment-related adverse effects. Several bio logical agents and small-molecule inhibitors targeting the signalling and growth pathways of rhabdomyosarcoma are in the pipeline, which hold promise for personalised therapy in the future. However, due to the rarity and molecular heterogenicity of the tumour, integrating these novel agents with the existing therapy would be a challenge.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Klíčová Slovamentioning

confidence: 99%

See 3 more Smart Citations

Rhabdomyosarcoma of the Gluteus Maximus – Case Report, Review of Literature and Emerging Therapeutic Targets

Meshram¹,

Kaur²,

Hura³

2019

Klin Onkol

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An Asymptomatic Verrucous Plaque on the Right Temple of an Adolescent Girl

Dai

Liu

2022

JAMA Dermatol

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An adolescent girl presented with an asymptomatic slightly reddish verrucous plaque on the right temple. The skin lesion was nail sized when first noticed 1½ years earlier, then gradually developed over the 8 months prior to presentation. The patient denied any associated fevers, weight loss, or night sweats. Physical examination revealed a slightly reddish verrucous mass with translucent papules and plaques on the right temple, about 5 cm in diameter, with surface hemorrhagic crust in the side adjacent to right eyebrow arch (Figure , A). The lesion was nontender with no purulent discharge and no severe necrotic changes. There was no hepatosplenomegaly or superficial lymphadenopathy. Laboratory tests, including blood cell counts, urinalysis, and kidney and hepatic panels, revealed no abnormalities. A skin biopsy was performed and submitted for histopathologic analysis (Figure , B-D). Diagnosis D. Primary cutaneous embryonal rhabdomyosarcomaClinical image A Original magnification ×40 B Original magnification ×400 C Immunohistochemical staining D Figure.A, A slightly reddish verrucous mass with translucent papules and plaques on the right temple. B, The histological examination showed papillomatous epidermal hyperplasia, edema of dermal papillae, and neoplastic infiltration consisting of small round blue cells with alternating areas of dense and loose cellularity (hematoxylin-eosin). C, Small, round blue cells were observed in the dermis with round, fusiform, or oval hyperchromatic nuclei, conspicuous nucleoli, and scant cytoplasm (hematoxylin-eosin). D, Tumor cells were positive for MyoD1 (original magnification ×400).

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Next‐generation sequencing reveals a novel role of lysine‐specific demethylase 1 in adhesion of rhabdomyosarcoma cells

Haydn

Kehr

Willmann

et al. 2019

Intl Journal of Cancer

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Lysine-specific demethylase 1 (LSD1), a histone lysine demethylase with the main specificity for H3K4me2, has been shown to be overexpressed in rhabdomyosarcoma (RMS) tumor samples. However, its role in RMS biology is not yet well understood. Here, we identified a new role of LSD1 in regulating adhesion of RMS cells. Genetic knockdown of LSD1 profoundly suppressed clonogenic growth in a panel of RMS cell lines, whereas LSD1 proved to be largely dispensable for regulating cell death and short-term survival. Combined RNA and ChIP-sequencing performed to analyze RNA expression and histone methylation at promoter regions revealed a gene set enrichment for adhesion-associated terms upon LSD1 knockdown. Consistently, LSD1 knockdown significantly reduced adhesion to untreated surfaces. Importantly, precoating of the plates with the adhesives collagen I or fibronectin rescued this reduced adhesion of LSD1 knockdown cells back to levels of control cells. Using KEGG pathway analysis, we identified 17 differentially expressed genes (DEGs) in LSD1 knockdown cells related to adhesion processes, which were validated by qRT-PCR. Combining RNA and ChIP-sequencing results revealed that, within this set of genes, SPP1, C3AR1, ITGA10 and SERPINE1 also exhibited increased H3K4me2 levels at their promoter regions in LSD1 knockdown compared to control cells. Indeed, LSD1 ChIP experiments confirmed enrichment of LSD1 at their promoter regions, suggesting a direct transcriptional regulation by LSD1. By identifying a new role of LSD1 in the modulation of cell adhesion and clonogenic growth of RMS cells, these findings highlight the importance of LSD1 in RMS.Additional Supporting Information may be found in the online version of this article.

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Rhabdomyosarcoma in children – current pathologic and molecular classification

Cited by 56 publications

References 17 publications

Rhabdomyosarcoma of the Gluteus Maximus – Case Report, Review of Literature and Emerging Therapeutic Targets

Rhabdomyosarcoma of the Gluteus Maximus – Case Report, Review of Literature and Emerging Therapeutic Targets

An Asymptomatic Verrucous Plaque on the Right Temple of an Adolescent Girl

Next‐generation sequencing reveals a novel role of lysine‐specific demethylase 1 in adhesion of rhabdomyosarcoma cells

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