Alterations of the RB1 gene in dedifferentiated liposarcoma

Takahira, Tomonari; Oda, Yoshinao; Tamiya, Sadafumi; Yamamoto, Hidetaka; Kobayashi, Chikashi; Izumi, Toshihiro; Ito, Kensaku; Iwamoto, Yukihide; Tsuneyoshi, Masazumi

doi:10.1038/modpathol.3800447

Cited by 27 publications

(21 citation statements)

References 30 publications

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“…Each row represents a single chromosomal subregion, each column shows the chromosomal status for a single tumour sample. Selected, cluster-associated chromosomal subregions are indicated on the right gested an association between dedifferentiation and the altered expression of specific proteins such as MDM2, p53, H-ras, β-catenin, and retinoblastoma protein [12,[26][27][28][29]. Also, chromosomal imbalances additionally to overrepresent 12q13-q15 were more frequent in DDLS than in WDLS [19].…”

Section: Discussionmentioning

confidence: 99%

Genomic profiling reveals subsets of dedifferentiated liposarcoma to follow separate molecular pathways

et al. 2009

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With the aim to provide more insight into their biology, a series of 79 liposarcomas (LS) representative of all main subtypes was analysed for chromosomal imbalances using comparative genomic hybridization. Based on the genetic data, unsupervised hierarchical clustering unveiled two main LS clusters, each with two subclusters, one comprising three subsets. The first main cluster consisted of one larger subcluster, being characterised by gains/high-level amplifications of chromosomal subregions 12q13-q15, and exclusively included well-differentiated and dedifferentiated LS. A smaller subcluster was set apart on the basis of recurrent gains of 20q13 and 8q24, and mainly comprised pleomorphic and myxoid/round cell LS. The larger subcluster was subdivided into three subsets, one with nearly exclusive overrepresentations of 12q13-q15, the second with additional frequent gains of 1q21-q24, and the third with further recurrent overrepresentations of 6q22-q24, 20q13, and 12q24 and frequent losses of 13q14-q21 and 11q22-q23. While the first subset comprised both well-differentiated and dedifferentiated LS, the second and third subsets entirely included dedifferentiated LS. The second main cluster was characterised by recurrent overrepresentations of 5p13-p15, 1q21-q24, 1p12-p21, and 17p11.2-p12 and essentially comprised pleomorphic and myxoid/round cell LS. A separation of this second main cluster into two subclusters was based on additional gains on 22q13 and losses on 1q42-q43. Genomic profiling reveals genetically distinct subsets of dedifferentiated LS, which are clearly different from pleomorphic, myxoid/round cell, and, for some subsets, from well-differentiated LS. These data indicate that dedifferentiated LS follow separate tumourigenic pathways and that genetic analysis is important to unravel these differences.

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Section: Discussionmentioning

confidence: 99%

Genomic profiling reveals subsets of dedifferentiated liposarcoma to follow separate molecular pathways

et al. 2009

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“…The forward primer was end-labeled with 6-carboxyXuorescein (6-FAM) at the 5Ј end. The procedure was carried out according to a method described previously (Takahira et al 2005). The data which were processed using GeneScan software (Applied Biosystems) were compared between the tumor and normal DNA for each patient.…”

Section: Allelic Imbalance Analysismentioning

confidence: 99%

Alterations of RB1 gene in embryonal and alveolar rhabdomyosarcoma: special reference to utility of pRB immunoreactivity in differential diagnosis of rhabdomyosarcoma subtype

Kohashi

Oda

Yamamoto

et al. 2008

J Cancer Res Clin Oncol

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“…Synovial sarcoma RT-PCR Poor prognosis (7) , high proliferative rate (8) PAX3-FKHR Alveolar RMS RT-PCR Poor prognosis (2) Tumor-suppressor genes p53 and MDM2 coexpression Mixed STS IHC Poor prognosis (9) Dedifferentiated LS IHC Dedifferentiation (10) p53 Mixed STS IHC Poor prognosis (11) Mixed STS Mutation Poor prognosis (12) Leiomyosarcoma IHC, mutation Poor prognosis in deep tumor (13) Synovial sarcoma IHC Poor prognosis (14) Myxoid/round cell LS IHC Poor prognosis (15) Myxoid/round cell LS IHC, mutation High histological grade, poor prognosis (16) ES/PNET IHC Poor prognosis (17) DFSP Mutation Malignant transformation to fibrosarcoma (18) MDM2 mRNA Mixed STS qRT-PCR Poor prognosis (19) p16 INK4a Leiomyosarcoma IHC Poor prognosis (20) p14 ARF Myxoid/round cell LS IHC Poor prognosis (16) RB Dedifferentiated LS IHC, LOH, mutation Dedifferentiation (21) DAP kinase, p53 Leiomyosarcoma MSP, mutation High histological grade, poor prognosis (22) RASSF1A Mixed STS MSP Poor prognosis, frequent in leiomyosarcoma (23) Cell cycle regulators CHFR MPNST IHC Poor prognosis (24) p21 WAF1 Myxofibrosarcoma IHC High histological grade, poor prognosis (25) Growth factors and receptors EGFR Mixed STS IHC Poor prognosis (26) HGF/MET coexpression Synovial sarcoma IHC Poor prognosis (27) Multidrug resistance P-glycoprotein Mixed STS IHC Poor prognosis (28) Mixed STS IHC Poor response to chemotherapy (29) Mixed STS IHC Large tumor size, high stage (30) MDR1/MRP1, coexpression…”

Section: Ss18-ssx1mentioning

confidence: 99%

“…2). (21) Malignant peripheral nerve sheath tumor often occurs in association with NF-1. We compared immunohistochemical p53 expression between MPNST and its concordant neurofibroma.…”

Section: Ss18-ssx1mentioning

confidence: 99%

Recent advances in the molecular pathology of soft tissue sarcoma: Implications for diagnosis, patient prognosis, and molecular target therapy in the future

Oda

Tsuneyoshi

2009

Cancer Science

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In the present paper, recent advances in the molecular pathology of soft tissue sarcomas (STS) and the implications for their prognostic value are reviewed, and the potential targets of molecular therapy are discussed. According to the molecular genetic aspect, STS are divided into two groups: chromosome translocation-associated sarcomas and sarcomas without specific translocation. In the former group, specific fusion transcripts, such as SS18-SSX, EWS-FLI1, and PAX3-FKHR, could be detected in synovial sarcoma, Ewing's sarcoma and primitive neuroectodermal tumor, and alveolar rhabdomyosarcoma, respectively. The direct or indirect interactions between these fusion transcripts and cell cycle regulators have been elucidated by several investigators. Therefore, these fusion transcripts are promising candidates as molecular targets. As evaluated in carcinomas, alterations of several tumor-suppressor genes and adhesion molecules and overexpression of growth factors and their receptors have been extensively assessed in STS. In mixed-type STS, epidermal growth factor receptor overexpression was associated with decreased overall survival, suggesting the beneficial role of epidermal growth factor receptor inhibitors in STS. In malignant rhabdoid tumor and epithelioid sarcoma, frequent alteration of the SMARCB1/INI1 tumor-suppressor gene and the loss of its protein have been demonstrated, indicating that this molecule could be an effective target of these sarcomas. In sarcomas with epithelioid differentiation, such as synovial sarcoma and epithelioid sarcoma, overexpression of dysadherin, which downregulates E-cadherin expression, was a poor prognostic factor. In conclusion, further studies are necessary to search for effective and specific molecules for the inhibition of tumor growth in each type of STS, especially in sarcomas without specific translocation. (Cancer Sci 2009; 100: 200-208) S oft tissue sarcomas are relatively rare malignant neoplasms compared with carcinomas and other neoplasms, and they constitute less than 1% of all cancers. STS are composed of many histological subtypes, such as pleomorphic undifferentiated sarcoma or malignant fibrous histiocytoma, leiomayosarcoma, and liposarcoma. In addition to their wide variety of subtypes, it is often difficult to make an accurate histological diagnosis because certain kinds of STS share similar morphological features. However, it is important to make a definitive diagnosis so that adequate therapy can be administered in each case. Recently, several reciprocal chromosomal translocations and fusion transcripts have been proven to be characteristic of particular histological types (Table 1; Fig. 1). The detection of these fusion transcripts is useful for the differential diagnosis of histologically peculiar cases.In relapsed cases of STS complete remission is difficult, despite the conventional multidisciplinary therapy. Therefore, novel therapies such as molecular target therapy are required, especially in relapsed cases. Several investigators have analyzed tumor-...

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Alterations of the RB1 gene in dedifferentiated liposarcoma

Cited by 27 publications

References 30 publications

Genomic profiling reveals subsets of dedifferentiated liposarcoma to follow separate molecular pathways

Genomic profiling reveals subsets of dedifferentiated liposarcoma to follow separate molecular pathways

Alterations of RB1 gene in embryonal and alveolar rhabdomyosarcoma: special reference to utility of pRB immunoreactivity in differential diagnosis of rhabdomyosarcoma subtype

Recent advances in the molecular pathology of soft tissue sarcoma: Implications for diagnosis, patient prognosis, and molecular target therapy in the future

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