Chromosome 17 loss-of-heterozygosity studies in benign and malignant tumors in neurofibromatosis type 1

Rasmussen, Sonja A.; Overman, Jennifer; Thomson, Susanne; Colman, Steven D.; Abernathy, C. R.; Trimpert, Rachael E.; Moose, Rebecca; Virdi, Gurinder; Roux, Kyle J.; Bauer, Mislen; Rojiani, Amyn M.; Maria, Bernard L.; Muir, David; Wallace, Margaret R.

doi:10.1002/1098-2264(200008)28:4<425::aid-gcc8>3.0.co;2-e

Cited by 97 publications

(39 citation statements)

References 34 publications

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“…Rasmussen and colleagues 22 determined that NF1 gene LOH was present in 13% of dermal neurofibromas, 40% of plexiform neurofibromas, and 60% of malignant peripheral nerve sheath tumours. In the LOH studies, three polymorphic markers were used.…”

Section: Discussionmentioning

confidence: 99%

NF1 gene loss of heterozygosity and expression analysis in sporadic colon cancer

Čačev

Radošević²,

Spaventi³

et al. 2005

Gut

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Section: Discussionmentioning

confidence: 99%

NF1 gene loss of heterozygosity and expression analysis in sporadic colon cancer

Čačev

Radošević²,

Spaventi³

et al. 2005

Gut

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“…Similarly, approximately 40–60% of sporadic MPNST harbor a somatic mutation in the NF1 gene (5, 6, 8) and 43% have loss of neurofibromin expression (7), supporting an important role for the NF1 tumor suppressor gene in the development of both sporadic and NF1-associated MPNSTs. While NF1 loss is required for MPNST development, it is not sufficient for malignant transformation.…”

Section: Introductionmentioning

confidence: 98%

Whole Exome Sequencing Reveals the Order of Genetic Changes during Malignant Transformation and Metastasis in a Single Patient with NF1-plexiform Neurofibroma

Hirbe

Dahiya

Miller

et al. 2015

Clinical Cancer Research

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Purpose Malignant peripheral nerve sheath tumors (MPNSTs) occur at increased frequency in individuals with neurofibromatosis type 1 (NF1), where they likely arise from benign plexiform neurofibroma precursors. While previous studies have employed a variety of discovery approaches to discover genes associated with MPNST pathogenesis, it is currently unclear what molecular events are associated with the evolution of MPNST from plexiform neurofibroma. Experimental Design Whole exome sequencing was performed on biopsy materials representing plexiform neurofibroma (n=3), MPNST, and metastasis from a single individual with NF1 over a 14-year period. Additional validation cases were used to assess candidate genes involved in malignant progression, while a murine MPNST model was employed for functional analysis. Results There was an increasing proportion of cells with a somatic NF1 gene mutation as the tumors progressed from benign to malignant, suggesting a clonal process in MPNST development. Copy number variations, including loss of one copy of the TP53 gene, were identified in the primary tumor and the metastatic lesion, but not in benign precursor lesions. A limited number of genes with non-synonymous somatic mutations (βIII-spectrin and ZNF208) were discovered, several of which were validated in additional primary and metastatic MPNST samples. Lastly, increased βIII-spectrin expression was observed in the majority of MPNSTs, and shRNA-mediated knockdown reduced murine MPNST growth in vivo. Conclusion Collectively, the ability to track the molecular evolution of MPNST in a single individual with NF1 offers new insights into the sequence of genetic events important for disease pathogenesis and progression for future mechanistic study.

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“…1 Children with NF1 have an increased risk of developing myeloid disease, particularly juvenile chronic myeloid leukaemia. Some 30-40% of NF1 patients develop plexiform neurofibromas 2-4 that become MPNSTs in 5-10% of cases, [5][6][7] often in pre-existing plexiform neurofibromas.…”

mentioning

confidence: 99%

Evaluation of genotype-phenotype correlations in neurofibromatosis type 1

Castle

2003

Journal of Medical Genetics

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Chromosome 17 loss-of-heterozygosity studies in benign and malignant tumors in neurofibromatosis type 1

Cited by 97 publications

References 34 publications

NF1 gene loss of heterozygosity and expression analysis in sporadic colon cancer

NF1 gene loss of heterozygosity and expression analysis in sporadic colon cancer

Whole Exome Sequencing Reveals the Order of Genetic Changes during Malignant Transformation and Metastasis in a Single Patient with NF1-plexiform Neurofibroma

Evaluation of genotype-phenotype correlations in neurofibromatosis type 1

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