Genetics of human malignant peripheral nerve sheath tumors

Pemov, Alexander; Li, Hua; Presley, William; Wallace, Margaret R.; Miller, David T.

doi:10.1093/noajnl/vdz049

Cited by 42 publications

(47 citation statements)

References 100 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have indicated that mutations affecting NF1, TP53, CDKN2A, PTEN and genes encoding components of PRC2 are the most common mutations that occur in MPNSTs regardless of whether they are www.nature.com/scientificreports/ NF1-associated, radiation-induced or sporadic [62][63][64][65][66] . Although NF1 and genes encoding PRC2 components are intact in 2XSB cells, these cells did have mutations in TP53, CDKN2A and PTEN, three genes which have been previously found to be mutated in both NF1-associated and sporadic MPNSTs 1,[67][68][69][70] . The TP53 (c.532C > G, exon 5, H178D; LOH) mutation [previously found in breast, genital tract, ovary, endometrial and lung cancers (COSMIC)] and homozygous CDKN2A loss that we identified in 2XSB cells promote genomic instability and loss of cell cycle checkpoints in other cancer types.…”

Section: Discussionmentioning

confidence: 79%

Establishment and genomic characterization of a sporadic malignant peripheral nerve sheath tumor cell line

Longo

Brosius

Znoyko

et al. 2021

Sci Rep

View full text Add to dashboard Cite

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive Schwann cell-derived neoplasms that occur sporadically or in patients with neurofibromatosis type 1 (NF1). Preclinical research on sporadic MPNSTs has been limited as few cell lines exist. We generated and characterized a new sporadic MPNST cell line, 2XSB, which shares the molecular and genomic features of the parent tumor. These cells have a highly complex karyotype with extensive chromothripsis. 2XSB cells show robust invasive 3-dimensional and clonogenic culture capability and form solid tumors when xenografted into immunodeficient mice. High-density single nucleotide polymorphism array and whole exome sequencing analyses indicate that, unlike NF1-associated MPNSTs, 2XSB cells have intact, functional NF1 alleles with no evidence of mutations in genes encoding components of Polycomb Repressor Complex 2. However, mutations in other genes implicated in MPNST pathogenesis were identified in 2XSB cells including homozygous deletion of CDKN2A and mutations in TP53 and PTEN. We also identified mutations in genes not previously associated with MPNSTs but associated with the pathogenesis of other human cancers. These include DNMT1, NUMA1, NTRK1, PDE11A, CSMD3, LRP5 and ACTL9. This sporadic MPNST-derived cell line provides a useful tool for investigating the biology and potential treatment regimens for sporadic MPNSTs.

show abstract

Section: Discussionmentioning

confidence: 79%

Establishment and genomic characterization of a sporadic malignant peripheral nerve sheath tumor cell line

Longo

Brosius

Znoyko

et al. 2021

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Genomic studies identified previously unrecognized critical involvement of PRC2 core components SUZ12 and EED in transition to malignancy. MPNSTs carry a relatively low burden of single nucleotide variants but consistently display a high number of structural copy number variants [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Malignant Glandular Triton Tumor Arising in the Radial Nerve with Prolonged Survival: A Case Report and Review of the Literature

AlAli

Amr

2021

Case Reports in Pathology

View full text Add to dashboard Cite

Divergent differentiation is a well-known phenomenon in malignant peripheral nerve sheath tumors (MPNST) which occurs approximately in 15% of these tumors, usually towards mesenchymal elements. Differentiation towards epithelial components, however, is quite uncommon, and even exceptionally rare is concomitant mesenchymal and glandular differentiation. To our knowledge, only 14 cases of MPNST with both mesenchymal (rhabdomyoblastic) and glandular differentiation had been reported, and only two of these tumors had frankly malignant glandular components. Herein, we report the third such case. A 26-year-old male, without any of the stigmata of NF1, presented with a 2-year history of pain in his left shoulder and an elbow swelling of six-month duration. The tumor was initially diagnosed clinically as a neurofibroma at a local hospital. The patient underwent excision of the mass there, and pathological examination at that hospital showed the tumor to be MPNST. Six months later, the patient was referred to our hospital, a tertiary care medical center, with recurrent swelling at the same location. Histopathological material from the referral hospital was reviewed, and the tumor was diagnosed as MPNST with rhabdomyoblastic differentiation or malignant triton tumor (MTT) that contained in addition foci of malignant glandular epithelium. The patient refused any surgical intervention. He received three cycles of chemotherapy followed by radiotherapy with excellent response and marked reduction in the size of the tumor. The patient had prolonged survival for 10 years following the initial resection of the tumor.

show abstract

“…Immunohistochemical loss of SMARCB1 (BAF47)/INI1 expression was found in 70% of cases [ 92 ]. The switch/sucrose nonfermentable (SWI/SNF) complex is a highly conserved multi-subunit complex of proteins encoded by numerous genes mapped to different chromosomal regions.…”

Section: Malignant Peripheral Nerve Sheath Tumors (Mpnsts)mentioning

confidence: 99%

Toward a Personalized Therapy in Soft-Tissue Sarcomas: State of the Art and Future Directions

Montella¹,

Altucci

Sarno

et al. 2021

Cancers

View full text Add to dashboard Cite

Soft-tissue sarcomas are rare tumors characterized by pathogenetic, morphological, and clinical intrinsic variability. Median survival of patients with advanced tumors are usually chemo- and radio-resistant, and standard treatments yield low response rates and poor survival results. The identification of defined genomic alterations in sarcoma could represent the premise for targeted treatments. Summarizing, soft-tissue sarcomas can be differentiated into histotypes with reciprocal chromosomal translocations, with defined oncogenic mutations and complex karyotypes. If the latter are improbably approached with targeted treatments, many suggest that innovative therapies interfering with the identified fusion oncoproteins and altered pathways could be potentially resolutive. In most cases, the characteristic genetic signature is discouragingly defined as “undruggable”, which poses a challenge for the development of novel pharmacological approaches. In this review, a summary of genomic alterations recognized in most common soft-tissue sarcoma is reported together with current and future therapeutic opportunities.

show abstract

Genetics of human malignant peripheral nerve sheath tumors

Cited by 42 publications

References 100 publications

Establishment and genomic characterization of a sporadic malignant peripheral nerve sheath tumor cell line

Establishment and genomic characterization of a sporadic malignant peripheral nerve sheath tumor cell line

Malignant Glandular Triton Tumor Arising in the Radial Nerve with Prolonged Survival: A Case Report and Review of the Literature

Toward a Personalized Therapy in Soft-Tissue Sarcomas: State of the Art and Future Directions

Contact Info

Product

Resources

About