Detection of COL1A1-PDGFB fusion transcripts and PDGFB/PDGFRB mRNA expression in dermatofibrosarcoma protuberans

Takahira, Tomonari; Oda, Yoshinao; Tamiya, Sadafumi; Higaki, Koichi; Kobayashi, Chikashi; Izumi, Toshihiro; Tateishi, Naomi; Iwamoto, Yukihide; Tsuneyoshi, Masazumi

doi:10.1038/modpathol.3800783

Cited by 56 publications

(49 citation statements)

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“…9 These molecular abnormalities are detectable by FISH or by reverse-transcription PCR (RT-PCR). 8,10,11,22 Given the variability of COL1A1 gene breakpoints, RT-PCR is difficult to perform on paraffin-embedded samples and FISH remains the most appropriate method in routine practice.…”

Section: Discussionmentioning

confidence: 99%

“…12 This rate is lower in a series of 57 cases, but this series was based on cases without histological review. 11 Other chromosomal rearrangements have been described in rare cases of dermatofibrosarcoma protuberans, including translocations t(5;8), t(9;22), t(2;17), and t(X;7). 18,[23][24][25] FISH analysis allowed to identify those cases with a certain diagnosis lacking the COL1A1/PDGFB-specific translocation.…”

Section: Discussionmentioning

confidence: 99%

“…[8][9][10][11][12] This abnormality involves the chromosomes 17 and 22, and forms the fusion gene collagen type-1 alpha 1 (COL1A1)-platelet-derived growth factor b (PDGFB). 1,5,[13][14] This rearrangement can be detected by fluorescence in situ hybridization (FISH) analysis.…”

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Fluorescence in situ hybridization analysis is a helpful test for the diagnosis of dermatofibrosarcoma protuberans

et al. 2015

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Cytogenetically, most dermatofibrosarcoma protuberans are characterized by chromosomal rearrangements resulting in the collagen type-1 alpha 1 (COL1A1)-platelet-derived growth factor b (PDGFB) fusion gene. This abnormality can be detected by fluorescence in situ hybridization (FISH) analysis in routine practice. The aim of this study was to evaluate the role of the FISH analysis in the diagnosis of dermatofibrosarcoma protuberans. A FISH analysis was prospectively and systematically performed on a series of 448 consecutive tumor specimens. All cases were reviewed by two independent pathologists and classified in three categories according to the probability of a DFSP diagnosis before molecular analyses. Cases were classified as certain when dermatofibrosarcoma protuberans was the only possible diagnosis. Those cases for which dermatofibrosarcoma protuberans remained the first diagnosis, but other differential diagnosis existed, were regarded as probable. When dermatofibrosarcoma protuberans was considered a differential diagnosis, they were labeled as possible. The final diagnosis was supported by clinicopathological findings and results of FISH analyses. Immunohistochemical analysis of CD34 was systematically performed, and additional markers when necessary. The cases (n ¼ 37) with a non-interpretable FISH were excluded. For the 185 certain tumors specimens: 178 (96%) FISH analyses showed a PDGFB/COL1A1 rearrangement, 7 (4%) were negative. For the 114 probable tumors specimens: 104 (91%) FISH analyses were positive and 10 (9%) were negative leading to a new diagnosis in 8 cases. For the 112 possible cases: 91 (81%) FISH analyses were negative and 21 (19%) were positive. Of the 21 cases, initial diagnoses included unclassified sarcoma, myxofibrosarcoma, dermatofibroma, reactive lesion, solitary fibrous tumor, perineurioma, benign nerve sheath tumor, and undifferentiated spindle cell tumor without malignant evidence. FISH analysis has been helpful for confirming the diagnosis of dermatofibrosarcoma protuberans in 25% (104/411) of cases and necessary for the diagnosis of dermatofibrosarcoma protuberans in 5% (21/411) of cases.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Fluorescence in situ hybridization analysis is a helpful test for the diagnosis of dermatofibrosarcoma protuberans

et al. 2015

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“…A characteristic feature of DFSP is the presence of a speciWc cytogenetic abnormality: more than 90% of DFSP possess supernumerary ring chromosomes or a unique translocation involving chromosomes 17 and 22 t(17;22) (22;q13) (Naeem et al 1995;Simon et al 1997;O'Brien et al 1998;Nishio et al 2001;Sirvent et al 2003;Takahira et al 2007;Patel et al 2008) which fuses the strongly expressed collagen type 1 alpha 1 (COL1A1) gene on chromosome 17 with the platelet-derived growth factor B-chain gene (PDGFB) on chromosome 22. PDGFB encodes the B-chain of PDGF, a ligand for the cell-surface located tyrosine kinase PDGF receptor (PDGFR).…”

Section: Molecular Tumor Pathogenesismentioning

confidence: 99%

Current treatment options in dermatofibrosarcoma protuberans

Lemm

Mügge

Mentzel

et al. 2009

J Cancer Res Clin Oncol

222

220

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Dermatofibrosarcoma protuberans (DFSP) is a rare malignant dermal neoplasm characterized by slow infiltrative growth, little metastatic potential but a high tendency to recur locally after surgical excision. DFSP is associated with a high cure rate. The optimal therapy is complete surgical resection. The recurrence potential of DFSP is directly related to the extent of resection. The need for wide excision margins has been amply documented. Wide local excision is a frequently used practice. Mohs micrographic surgery with continuous histological margin control is further propagated to reduce local recurrence rates. In more than 90% of DFSP, a specific chromosomal aberration is described, involving Chromosomes 17 and 22. It leads to a constitutive activation of the platelet-derived growth factor receptor (PDGFR) followed by continuous stimulation of the tumor cell growth. The use of targeted inhibitors of PDGFR is a good therapeutic option in the treatment strategy of unresectable locally advanced, recurrent or metastatic disease. With Imatinib, a selective PDGFR tyrosin kinase inhibitor, partial and complete remissions of DFSP could be achieved. This article reviews the current opinion and literature about DFSP and resulting therapy strategies.

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“…We recently demonstrated PDGFB gene amplification and coexpression of PDGFB and PDGFRB mRNA in tumor tissue of DFSP. (3) Moreover, the PDGFB and PDGFRB mRNA expression levels showed a positive correlation. These results indicate that the COL1A1-PDGFB fusion protein, which is processed by the COL1A1-PDGFB transcript, can serve as a functional ligand for PDGFRB in DFSP.…”

Section: Growth Factors and Their Receptorsmentioning

confidence: 90%

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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Detection of COL1A1-PDGFB fusion transcripts and PDGFB/PDGFRB mRNA expression in dermatofibrosarcoma protuberans

Cited by 56 publications

References 28 publications

Fluorescence in situ hybridization analysis is a helpful test for the diagnosis of dermatofibrosarcoma protuberans

Fluorescence in situ hybridization analysis is a helpful test for the diagnosis of dermatofibrosarcoma protuberans

Current treatment options in dermatofibrosarcoma protuberans

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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