Pediatric Rhabdomyosarcoma: Epidemiology and Genetic Susceptibility

Martin-Giacalone, Bailey A.; Weinstein, P. Adam; Plon, Sharon E.; Lupo, Philip J.

doi:10.3390/jcm10092028

Cited by 46 publications

(46 citation statements)

References 101 publications

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“…35 In rhabdomyosarcoma, nominal enrichment signal was observed for TP53 and DICER1, genes that have previously been implicated in germline predisposition to pediatric rhabdomyosarcoma. 36 We were able to redemonstrate a nominal enrichment signal for BRCA2 (MIM: 600185), a gene with a previous moderate level of evidence for a role in germline predisposition to rhabdomyosarcoma. 33,[37][38][39] We also observed a nominal enrichment signal in SDHD (MIM: 602690); pathogenic germline variants in succinate dehydrogenase complex genes have been reported in rhabdomyosarcoma and other sarcoma subtypes before.…”

Section: Ancestry Composition Of Discovery Cohortmentioning

confidence: 83%

Germline predisposition to pediatric Ewing sarcoma is characterized by inherited pathogenic variants in DNA damage repair genes

Gillani

Camp

Han

et al. 2022

The American Journal of Human Genetics

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Section: Ancestry Composition Of Discovery Cohortmentioning

confidence: 83%

Germline predisposition to pediatric Ewing sarcoma is characterized by inherited pathogenic variants in DNA damage repair genes

Gillani

Camp

Han

et al. 2022

The American Journal of Human Genetics

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“…Rhabdomyosarcoma (RMS) is another sarcoma classically driven by a fusion protein and exhibits strong LSD1 overexpression. RMS is the most common soft tissue sarcoma in children, and is subdivided into alveolar and embryonal rhabdomyosarcoma based on the histological makeup of the tumor ( 66 ). About 31% are alveolar and present with an alveolar pattern on histology, and 58% are embryonal with sheets and nests on histology, while the remaining 11% are made up of smaller subtypes with other histological patterns ( 66 ).…”

Section: Lsd1 In Sarcomasmentioning

confidence: 99%

Lysine specific demethylase 1 is a molecular driver and therapeutic target in sarcoma

Dreher

Theisen

2023

Front. Oncol.

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Sarcomas are a diverse group of tumors with numerous oncogenic drivers, and display varied clinical behaviors and prognoses. This complexity makes diagnosis and the development of new and effective treatments challenging. An incomplete understanding of both cell of origin and the biological drivers of sarcomas complicates efforts to develop clinically relevant model systems and find new molecular targets. Notably, the histone lysine specific demethylase 1 (LSD1) is overexpressed in a number of different sarcomas and is a potential therapeutic target in these malignancies. With the ability to modify histone marks, LSD1 is a key player in many protein complexes that epigenetically regulate gene expression. It is a largely context dependent enzyme, having vastly different and often opposing roles depending on the cellular environment and which interaction partners are involved. LSD1 has been implicated in the development of many different types of cancer, but its role in bone and soft tissue sarcomas remains poorly understood. In this review, we compiled what is known about the LSD1 function in various sarcomas, to determine where knowledge is lacking and to find what theme emerge to characterize how LSD1 is a key molecular driver in bone and soft tissue sarcoma. We further discuss the current clinical landscape for the development of LSD1 inhibitors and where sarcomas have been included in early clinical trials.

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“…Other authors have shown that DICER1 variants, either somatic or germline, occur almost ubiquitously across all uterine embryonal RMS [21] . The majority of DICER1-associated RMS have been reported in the female genitourinary tract, but an association with ERMS outside of this body system is emerging [22,23] .…”

Section: Rhabdomyosarcomamentioning

confidence: 99%

Germline predisposition to soft tissue sarcoma

Vagher¹,

Dietz²,

Schiffman³

et al. 2022

J Cancer Metastasis Treat

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Soft tissue sarcoma (STS) most often occurs sporadically, but can also arise in the setting of a germline cancer predisposition syndrome (CPS). There is significant diversity amongst STS diagnoses as these tumors exhibit a variety of histologies, occur in all age groups, and can occur in any location in the body. This diversity is also reflected in the many known associated germline cancer predisposition associations. Some STS diagnoses, such as anaplastic rhabdomyosarcoma, are associated with high heritability and other STS, such as Ewing sarcoma, are notably absent from known CPS. Recognizing when a STS is more likely to be hereditary can influence clinical management. Individuals diagnosed with STS due to CPS may be at risk for other malignancies and should undergo additional surveillance for early detection. Additionally, family members should undergo genetic testing as they also may be at risk to develop STS and other CPS-associated malignancies. Some underlying cancer predisposition diagnoses may have implications for the treatment of a concurrent malignancy as in the case of PARP inhibitor therapy in the setting of homologous recombination deficiency. This review summarizes current knowledge of selected STS and their associations with CPS.

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Pediatric Rhabdomyosarcoma: Epidemiology and Genetic Susceptibility

Cited by 46 publications

References 101 publications

Germline predisposition to pediatric Ewing sarcoma is characterized by inherited pathogenic variants in DNA damage repair genes

Germline predisposition to pediatric Ewing sarcoma is characterized by inherited pathogenic variants in DNA damage repair genes

Lysine specific demethylase 1 is a molecular driver and therapeutic target in sarcoma

Germline predisposition to soft tissue sarcoma

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