Further evidence of the increased risk for malignant peripheral nerve sheath tumour from a Scottish cohort of patients with neurofibromatosis type 1

McCaughan, Jennifer; Holloway, Susan; Davidson, Rosemary; Lam, Wayne

doi:10.1136/jmg.2006.048140

Cited by 90 publications

(56 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…22,23,29,30 Malignant peripheral nerve sheath tumors are the most frequent malignant neoplasms associated with NF1, occurring sometime in the life of ϳ10% of affected individuals. 6,[31][32][33][34] These malignancies tend to develop at a much younger age and have a poorer prognosis for survival in people with NF1 than in the general population. 31,[33][34][35] Malignant peripheral nerve sheath tumors are rare in children and adolescents with NF1, tend to be of low grade, and may be difficult to distinguish from atypical plexiform neurofibromas in this age group.…”

Section: Other Neoplasmsmentioning

confidence: 99%

“…6,[31][32][33][34] These malignancies tend to develop at a much younger age and have a poorer prognosis for survival in people with NF1 than in the general population. 31,[33][34][35] Malignant peripheral nerve sheath tumors are rare in children and adolescents with NF1, tend to be of low grade, and may be difficult to distinguish from atypical plexiform neurofibromas in this age group. High-grade malignant peripheral nerve sheath tumors usually arise in patients with NF1 in their 20s or 30s.…”

Section: Other Neoplasmsmentioning

confidence: 99%

“…High-grade malignant peripheral nerve sheath tumors usually arise in patients with NF1 in their 20s or 30s. 31,33,34 Individuals with NF1 who have benign subcutaneous neurofibromas or benign internal plexiform neurofibromas appear to be at greater risk of developing malignant peripheral nerve sheath tumors than people with NF1 who lack such benign tumors. 16,36 Two to 3% of people with NF1 37 develop a diffuse polyneuropathy that may be associated with multiple nerve root neurofibromas and a high risk of developing malignant peripheral nerve sheath tumors.…”

Section: Other Neoplasmsmentioning

confidence: 99%

See 2 more Smart Citations

Clinical and genetic aspects of neurofibromatosis 1

Jett

Friedman

2010

Genetics in Medicine

412

382

View full text Add to dashboard Cite

Section: Other Neoplasmsmentioning

confidence: 99%

Section: Other Neoplasmsmentioning

confidence: 99%

Section: Other Neoplasmsmentioning

confidence: 99%

See 1 more Smart Citation

Clinical and genetic aspects of neurofibromatosis 1

Jett

Friedman

2010

Genetics in Medicine

412

382

View full text Add to dashboard Cite

“…At least a third of NF1 patients develop larger benign plexiform neurofibromas that cause disfigurement and morbidity when they compress vital structures. Surgical removal of neurofibromas is not always feasible due to tumor location, resulting in substantial morbidity for NF1 patients, and plexiform neurofibromas can transform to malignant peripheral nerve sheath tumors (MPNSTs), a leading cause of death in adults with NF1 (3)(4)(5)(6). There is currently no chemotherapeutic regimen that will effectively treat NF1 tumors, warranting investigation into the development of novel molecular-targeted therapeutic strategies (7).…”

Section: Introductionmentioning

confidence: 99%

MEK inhibition exhibits efficacy in human and mouse neurofibromatosis tumors

et al. 2012

View full text Add to dashboard Cite

Neurofibromatosis type 1 (NF1) patients develop benign neurofibromas and malignant peripheral nerve sheath tumors (MPNST). These incurable peripheral nerve tumors result from loss of NF1 tumor suppressor gene function, causing hyperactive Ras signaling. Activated Ras controls numerous downstream effectors, but specific pathways mediating the effects of hyperactive Ras in NF1 tumors are unknown. We performed crossspecies transcriptome analyses of mouse and human neurofibromas and MPNSTs and identified global negative feedback of genes that regulate Ras/Raf/MEK/ERK signaling in both species. Nonetheless, ERK activation was sustained in mouse and human neurofibromas and MPNST. We used a highly selective pharmacological inhibitor of MEK, PD0325901, to test whether sustained Ras/Raf/MEK/ERK signaling contributes to neurofibroma growth in a neurofibromatosis mouse model (Nf1 fl/fl ;Dhh-Cre) or in NF1 patient MPNST cell xenografts. PD0325901 treatment reduced aberrantly proliferating cells in neurofibroma and MPNST, prolonged survival of mice implanted with human MPNST cells, and shrank neurofibromas in more than 80% of mice tested. Our data demonstrate that deregulated Ras/ERK signaling is critical for the growth of NF1 peripheral nerve tumors and provide a strong rationale for testing MEK inhibitors in NF1 clinical trials.

show abstract

“…The major cornerstone of therapy for localized disease is surgery [7]. There are only a few reports on chemotherapy for unresectable or metastatic MPNST in the literature [8,9,10]. …”

Section: Introductionmentioning

confidence: 99%

Clinical Signs of Neurofibromatosis Impact on the Outcome of Malignant Peripheral Nerve Sheath Tumors

Lamm

Schur²,

Köstler³

et al. 2014

Oncology

View full text Add to dashboard Cite

Objective: Malignant peripheral nerve sheath tumors (MPNST) are a rare subtype of sarcoma, with a poor outcome. MPNST are regarded as being sporadic or associated with neurofibromatosis type 1 (NF1). Few comparative overall-survival (OS) data in these 2 subsets of MPNST patients exist. The aim of this retrospective study was to assess OS in sporadic and NF1-associated MPNST patients. Methods: Fourteen consecutive patients with initial localized as well as initial metastatic MPNST were diagnosed and treated in our department. Patients with sporadic MPNST were assigned to group A and those with NF1-associated MPNST to group B. Results: Eight versus 6 patients were allocated to groups A and B. Primary tumors were located on the extremities in all but 1 patient. Two patients in group A and 4 patients in group B experienced a relapse. Four patients died in each of the 2 groups. Median follow-up was 66.2 and 57.2 months in group A and group B, respectively. Median OS in group A was 46.9 months versus 12.7 months in group B. Conclusions: In this small, single-center study, sporadic-MPNST patients had a longer median OS than those with NF1-associated MPNST.

show abstract

Further evidence of the increased risk for malignant peripheral nerve sheath tumour from a Scottish cohort of patients with neurofibromatosis type 1

Cited by 90 publications

References 14 publications

Clinical and genetic aspects of neurofibromatosis 1

Clinical and genetic aspects of neurofibromatosis 1

MEK inhibition exhibits efficacy in human and mouse neurofibromatosis tumors

Clinical Signs of Neurofibromatosis Impact on the Outcome of Malignant Peripheral Nerve Sheath Tumors

Contact Info

Product

Resources

About