Computer-assisted cytogenetic analysis of 51 malignant peripheral-nerve-sheath tumors: SporadicVs. neurofibromatosis-type-1-associated malignant schwannomas

Plaat, Boudewijn E. C.; Molenaar, Willemina M.; Mastik, Mirjam F.; Hoekstra, Harald J.; Meerman, Gerard J. te; Berg, Eva van den

doi:10.1002/(sici)1097-0215(19991008)83:2<171::aid-ijc5>3.0.co;2-s

Cited by 57 publications

(3 citation statements)

References 30 publications

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“…The strongest candidate on devil chromosome 1 is NF2 . This hypothesis is based on the frequency of breakpoints in the region encompassing NF2 in humans (corresponding to 22q11-13) involved in MPNSTs 26 , 27 , and the role of the loss or inactivation of NF2 in Schwann cell tumours 28 . Although we were unable to isolate and map the NF2 gene as part of this study, we demonstrated that this region of the DFT1 genome has undergone rearrangement and even some deletion, including the deletion of one copy of the tumour suppressor LZTR1 29 (Fig.…”

Section: Discussionmentioning

confidence: 99%

Identification of candidate genes for devil facial tumour disease tumourigenesis

Taylor

Zhang

Schöning

et al. 2017

Sci Rep

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Devil facial tumour (DFT) disease, a transmissible cancer where the infectious agent is the tumour itself, has caused a dramatic decrease in Tasmanian devil numbers in the wild. The purpose of this study was to take a candidate gene/pathway approach to identify potentially perturbed genes or pathways in DFT. A fusion of chromosome 1 and X is posited as the initial event leading to the development of DFT, with the rearranged chromosome 1 material now stably maintained as the tumour spreads through the population. This hypothesis makes chromosome 1 a prime chromosome on which to search for mutations involved in tumourigenesis. As DFT1 has a Schwann cell origin, we selected genes commonly implicated in tumour pathways in human nerve cancers, or cancers more generally, to determine whether they were rearranged in DFT1, and mapped them using molecular cytogenetics. Many cancer-related genes were rearranged, such as the region containing the tumour suppressor NF2 and a copy gain for ERBB3, a member of the epidermal growth factor receptor family of receptor tyrosine kinases implicated in proliferation and invasion of tumours in humans. Our mapping results have provided strong candidates not previously detected by sequencing DFT1 genomes.

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Section: Discussionmentioning

confidence: 99%

Identification of candidate genes for devil facial tumour disease tumourigenesis

Taylor

Zhang

Schöning

et al. 2017

Sci Rep

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“…Despite this variability, some common patterns have been identified in the genomes of MPNSTs. MPNSTs often are hypodiploid or near triploid, with gains most often occurring in chromosome 7, 8q and 15q and losses evident in chromosomes 1p, 9p, 11, 12p, 14q, 17q, 18, 22q, X and Y [53][54][55][56][57][58][59][60][61] . In 2XSB cells and their parent tumor, we identified gains of chromosomes 7, 8 and 15q, which is consistent with these earlier studies.…”

Section: Discussionmentioning

confidence: 99%

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

Longo

Brosius

Znoyko

et al. 2021

Sci Rep

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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.

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“…In addition, there are also coincidental reports on cancer-associated amplification and/or imbalanced rearrangements involving other repetitive DNAs, such as Yq12 [ 42 , 43 ], 1q12 [ 44 , 45 , 46 , 47 ], and 9q12 [ 48 , 49 ]; in addition, mutations [ 29 ] and acrocentric p-arms have also been reported [ 29 , 35 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ].…”

Section: Chromosomal Heteromorphisms (Chs) and Cancermentioning

confidence: 99%

Chromosomal Heteromorphisms and Cancer Susceptibility Revisited

Liehr

2022

Cells

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Chromosomal heteromorphisms (CHs) are a part of genetic variation in man. The past literature largely posited whether CHs could be correlated with the development of malignancies. While this possibility seemed closed by end of the 1990s, recent data have raised the question again on the potential influences of repetitive DNA elements, the main components of CHs, in cancer susceptibility. Such new evidence for a potential role of CHs in cancer can be found in the following observations: (i) amplification and/or epigenetic alterations of CHs are routinely reported in tumors; (ii) the expression of CH-derived RNA in embryonal and other cells under stress, including cancer cells; (iii) the expression of parts of CH-DNA as long noncoding RNAs; plus (iv) theories that suggest a possible application of the “two-hit model” for euchromatic copy number variants (CNVs). Herein, these points are discussed in detail, which leads to the conclusion that CHs are by far not given sufficient consideration in routine cytogenetic analysis, e.g., leukemias and lymphomas, and need more attention in future research settings including solid tumors. This heightened focus may only be achieved by approaches other than standard sequencing or chromosomal microarrays, as these techniques are at a minimum impaired in their ability to detect, if not blind to, (highly) repetitive DNA sequences.

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Computer-assisted cytogenetic analysis of 51 malignant peripheral-nerve-sheath tumors: SporadicVs. neurofibromatosis-type-1-associated malignant schwannomas

Cited by 57 publications

References 30 publications

Identification of candidate genes for devil facial tumour disease tumourigenesis

Identification of candidate genes for devil facial tumour disease tumourigenesis

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

Chromosomal Heteromorphisms and Cancer Susceptibility Revisited

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