Clear cell sarcoma: The Roswell Park experience

Finley, Jennifer; Hanypsiak, Bryan T.; McGrath, Brian E.; Kraybill, William G.; Gibbs, John F.

doi:10.1002/jso.1057

Cited by 74 publications

(69 citation statements)

References 30 publications

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“…4 -8 Follow-up studies have shown that approximately 55% of patients die of their disease within 5 years after diagnosis. 5,7,8 Since CCS displays a number of histopathologic features that overlap with conventional malignant melanoma, there may be difficulties in the distinction between CCS and metastatic malignant melanoma with an unknown primary site. 2,9 Clonal chromosomal abnormalities have been described in 25 CCSs, and the translocation t(12;22)(q13;q12-13), detected in 17 of the cases, appears to be a characteristic rearrangement.…”

mentioning

confidence: 99%

Molecular genetic characterization of the EWS/ATF1 fusion gene in clear cell sarcoma of tendons and aponeuroses

Panagopoulos

Mertens

Dębiec‐Rychter

et al. 2002

Intl Journal of Cancer

141

119

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Clear cell sarcoma (CCS) is a rare malignant soft tissue tumor particularly associated with tendons and aponeuroses. The cytogenetic hallmark is the translocation t(12;22)(q13; q12) resulting in a chimeric EWS/ATF1 gene in which the 3 -terminal part of EWS at 22q is replaced by the 3 -terminal part of ATF1 at 12q. To date, only 13 cases of CCS have been analyzed for fusion genes at the transcription level, and there is no information about the breakpoints at the genomic level. In the present study, we describe the molecular genetic characteristics of CCS from 10 patients. Karyotypes were obtained from 10 cases, 7 of which showed the characteristic t(12;22). As an initial step in the characterization of the EWS/ATF1 and ATF1/EWS chimeras, we constructed an exon/ intron map of the ATF1 gene. The entire ATF1 gene spanned >40 kb and was composed of 7 exons. Intron 3, in which most of the genomic breakpoints occurred, was to a large extent (83%) composed of repetitive elements. RT-PCR amplified EWS/ATF1 cDNA fragments in all patients and ATF1/EWS cDNA fragments in 6 of 10 patients. Four types of EWS/ATF1 chimeric transcript, designated types 1-4, were identified. The most frequent chimeric transcript (type 1) was an inframe fusion of exon 8 of EWS with exon 4 of ATF1. This was the only chimeric transcript in 5 patients but found together with other variants in 3 tumors. The type 2 transcript of EWS/ATF1, an in-frame fusion of exon 7 of EWS with exon 5 of ATF1, was detected in 4 patients, as the only transcript in 1 case and together with other variants in 3 cases. An in-frame fusion of exon 10 of EWS with exon 5 of ATF1 (type 3) was found in 1 patient as the only transcript, and an out-of-frame fusion of EWS exon 7 with ATF1 exon 7 (type 4) was detected in 1 patient together with type 1 and type 2 transcripts. Sequencing of the amplified ATF1/EWS cDNA fragments showed in 5 patients that ATF1 exon 3 was fused with EWS exon 10, resulting in an out-of-frame chimeric transcript. In 1 case, nt 428 of ATF1 (exon 4) was fused with EWS exon 8; at the junction, there was an insertion of 4 nucleotides, also resulting in an out-of-frame transcript. Genomic extra long PCR and sequence analysis mapped the genomic breakpoints to introns 7, 8 and 9 of EWS and intron 3 and exon 4 of ATF1. While a simple end-to-end fusion was observed in 2 cases, additional nucleotides were found at the junctions in 2 other cases. In addition, topoisomerase I consensus sequences were found close to the junctions, suggesting that this enzyme may participate in the genesis of the EWS/ATF1 fusion.

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confidence: 99%

Molecular genetic characterization of the EWS/ATF1 fusion gene in clear cell sarcoma of tendons and aponeuroses

Panagopoulos

Mertens

Dębiec‐Rychter

et al. 2002

Intl Journal of Cancer

141

119

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“…Some previous reports have described the use of either chemotherapy or radiotherapy for treating clear cell sarcoma. However, the response rate to chemotherapy was 0-25% in these reports and the 5-year overall survival rate ranged from 55 to 68%, so these treatments had little impact [12][13][14][15][16] (Table 2).…”

Section: Discussionmentioning

confidence: 99%

Caffeine-potentiated chemotherapy for clear cell sarcoma: a report of five cases

et al. 2011

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Background Clear cell sarcoma is a rare malignant tumor of soft tissue which is most commonly encountered in the extremities, especially in the foot and ankle. This tumor is slow-growing and looks like a benign tumor; it is therefore often treated inadequately and its high rate of recurrence and metastases results in a poor prognosis. Caffeine has been used as a chemotherapy potentiator that inhibits DNA damage repair and enhances the cytocidal effects of anticancer drugs. This study reports the effect of caffeinepotentiated chemotherapy for clear cell sarcoma in five patients. Methods Caffeine-potentiated chemotherapy was administered to five patients with clear cell sarcoma. Three to five courses of intra-arterial chemotherapy using cisplatin, doxorubicin and caffeine were administered preoperatively, at 3-week intervals. Conservatively, wide margin surgery was performed following the preoperative chemotherapy. Intravenous cisplatin and doxorubicin with caffeine were administered three to six times to the patients who responded to the preoperative chemotherapy. This study evaluated the response to chemotherapy, recurrence, metastasis and the overall prognosis in these five patients.Results Four of the eligible patients responded to preoperative chemotherapy. Local recurrence occurred in only one of the five patients. Distant metastasis newly developed in one patient. All five patients survive. Conclusion Caffeine-potentiated chemotherapy can be effective treatment for clear cell sarcoma not only as initial therapy, but also as salvage therapy.

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“…However, melanoma only very rarely presents with a soft tissue metastasis in the absence of a detectable skin or mucous membrane tumor. In addition, the t(12;22)(q13;q12) translocation is pathognomonic of clear cell sarcoma of soft tissues; it does not occur in melanoma [5,7]. A clear cell sarcoma can occur at any age but predominantly affects female patients aged between 20 and 40 years [3,5,7,15].…”

Section: Discussion and Treatmentmentioning

confidence: 99%

“…In addition, the t(12;22)(q13;q12) translocation is pathognomonic of clear cell sarcoma of soft tissues; it does not occur in melanoma [5,7]. A clear cell sarcoma can occur at any age but predominantly affects female patients aged between 20 and 40 years [3,5,7,15]. Over 95% of all clear cell sarcomas are located in the extremities, with the foot and ankle affected in approximately 40% [3,4,7].…”

Section: Discussion and Treatmentmentioning

confidence: 99%

“…However, the small number of patients in these studies does not allow any firm conclusions and further research in this area is warranted. Another therapeutic option reported to have limited success in patients with advances states of clear cell sarcoma is isolated limb perfusion [5]. Local recurrence, regional lymph node metastasis, and distant metastasis, especially to lungs and bones, are common.…”

Section: Discussion and Treatmentmentioning

confidence: 99%

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