BCOR - CCNB3 Fusion Positive Sarcomas: A Clinicopathologic and Molecular Analysis of 36 Cases with Comparison to Morphologic Spectrum and Clinical Behavior of Other Round Cell Sarcomas

Yu-Chien Kao, Adepitan A. Owosho, Yun Shao Sung, Lei Zhang, Yumi Fujisawa, Jen Chieh Lee, Leonard Wexler, Pedram Argani, David Swanson, Brendan C. Dickson, Christopher D.M. Fletcher, Cristina R. Antonescu

研究成果: 雜誌貢獻文章

25 引文 (Scopus)

摘要

BCOR-CCNB3 sarcoma (BCS) is a recently defined genetic entity among undifferentiated round cell sarcomas, which was initially classified as and treated similarly to the Ewing sarcoma (ES) family of tumors. In contrast to ES, BCS shows consistent BCOR overexpression, and preliminary evidence suggests that these tumors share morphologic features with other tumors harboring BCOR genetic alterations, including BCOR internal tandem duplication (ITD) and BCOR-MAML3. To further investigate the pathologic features, clinical behavior, and their relationship to other round cell sarcomas, we collected 36 molecularly confirmed BCSs for a detailed histologic and immunohistochemical analysis. Four of the cases were also analyzed by RNA sequencing (RNAseq). An additional case with BCOR overexpression but negative CCNB3 abnormality showed a novel KMT2D-BCOR fusion by targeted RNAseq. The patients ranged in age from 2 to 44 years old (mean and median, 15), with striking male predominance (M:F=31:5). The tumor locations were slightly more common in bone (n=20) than soft tissue (n=14), with rare visceral (kidney, n=2) involvement. Histologically, BCS showed a spectrum of round to spindle cells with variable cellularity, monomorphic nuclei and fine chromatin pattern, delicate capillary network, and varying amounts of myxoid or collagenous stroma. The morphologic features and immunoprofile showed considerable overlap with other round cell sarcomas with BCOR oncogenic upregulation, that is, BCOR-MAML3 and BCOR ITD. Follow-up available in 22 patients showed a 5-year overall survival of 72%, which was relatively similar to ES (79%, P=0.738) and significantly better than CIC-DUX4 sarcomas (43%, P=0.005) control groups. Local recurrences occurred in 6 patients and distant metastases (lung, soft tissue/bone, pancreas) in 4. Seven of 9 cases treated with an ES chemotherapy regimen with evaluable histologic response showed >60% necrosis in posttherapy resections. Unsupervised clustering by RNAseq data revealed that tumors with BCOR genetic alterations, including BCOR-CCNB3, BCOR-MAML3, and BCOR ITD, formed a tight genomic group distinct from ES and CIC-rearranged sarcomas.

原文英語
頁(從 - 到)604-615
頁數12
期刊American Journal of Surgical Pathology
42
發行號5
DOIs
出版狀態已發佈 - 一月 1 2018

指紋

Sarcoma
Ewing's Sarcoma
RNA Sequence Analysis
Neoplasms
Bone and Bones
Chromatin
Cluster Analysis
Pancreas
Necrosis
Up-Regulation
Neoplasm Metastasis
Kidney
Recurrence
Drug Therapy
Lung
Control Groups
Survival

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

引用此文

BCOR - CCNB3 Fusion Positive Sarcomas : A Clinicopathologic and Molecular Analysis of 36 Cases with Comparison to Morphologic Spectrum and Clinical Behavior of Other Round Cell Sarcomas. / Kao, Yu-Chien; Owosho, Adepitan A.; Sung, Yun Shao; Zhang, Lei; Fujisawa, Yumi; Lee, Jen Chieh; Wexler, Leonard; Argani, Pedram; Swanson, David; Dickson, Brendan C.; Fletcher, Christopher D.M.; Antonescu, Cristina R.

於: American Journal of Surgical Pathology, 卷 42, 編號 5, 01.01.2018, p. 604-615.

研究成果: 雜誌貢獻文章

Kao, Yu-Chien ; Owosho, Adepitan A. ; Sung, Yun Shao ; Zhang, Lei ; Fujisawa, Yumi ; Lee, Jen Chieh ; Wexler, Leonard ; Argani, Pedram ; Swanson, David ; Dickson, Brendan C. ; Fletcher, Christopher D.M. ; Antonescu, Cristina R. / BCOR - CCNB3 Fusion Positive Sarcomas : A Clinicopathologic and Molecular Analysis of 36 Cases with Comparison to Morphologic Spectrum and Clinical Behavior of Other Round Cell Sarcomas. 於: American Journal of Surgical Pathology. 2018 ; 卷 42, 編號 5. 頁 604-615.
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abstract = "BCOR-CCNB3 sarcoma (BCS) is a recently defined genetic entity among undifferentiated round cell sarcomas, which was initially classified as and treated similarly to the Ewing sarcoma (ES) family of tumors. In contrast to ES, BCS shows consistent BCOR overexpression, and preliminary evidence suggests that these tumors share morphologic features with other tumors harboring BCOR genetic alterations, including BCOR internal tandem duplication (ITD) and BCOR-MAML3. To further investigate the pathologic features, clinical behavior, and their relationship to other round cell sarcomas, we collected 36 molecularly confirmed BCSs for a detailed histologic and immunohistochemical analysis. Four of the cases were also analyzed by RNA sequencing (RNAseq). An additional case with BCOR overexpression but negative CCNB3 abnormality showed a novel KMT2D-BCOR fusion by targeted RNAseq. The patients ranged in age from 2 to 44 years old (mean and median, 15), with striking male predominance (M:F=31:5). The tumor locations were slightly more common in bone (n=20) than soft tissue (n=14), with rare visceral (kidney, n=2) involvement. Histologically, BCS showed a spectrum of round to spindle cells with variable cellularity, monomorphic nuclei and fine chromatin pattern, delicate capillary network, and varying amounts of myxoid or collagenous stroma. The morphologic features and immunoprofile showed considerable overlap with other round cell sarcomas with BCOR oncogenic upregulation, that is, BCOR-MAML3 and BCOR ITD. Follow-up available in 22 patients showed a 5-year overall survival of 72{\%}, which was relatively similar to ES (79{\%}, P=0.738) and significantly better than CIC-DUX4 sarcomas (43{\%}, P=0.005) control groups. Local recurrences occurred in 6 patients and distant metastases (lung, soft tissue/bone, pancreas) in 4. Seven of 9 cases treated with an ES chemotherapy regimen with evaluable histologic response showed >60{\%} necrosis in posttherapy resections. Unsupervised clustering by RNAseq data revealed that tumors with BCOR genetic alterations, including BCOR-CCNB3, BCOR-MAML3, and BCOR ITD, formed a tight genomic group distinct from ES and CIC-rearranged sarcomas.",
keywords = "BCOR, CCNB3, Ewing sarcoma, fusions, round cell sarcoma",
author = "Yu-Chien Kao and Owosho, {Adepitan A.} and Sung, {Yun Shao} and Lei Zhang and Yumi Fujisawa and Lee, {Jen Chieh} and Leonard Wexler and Pedram Argani and David Swanson and Dickson, {Brendan C.} and Fletcher, {Christopher D.M.} and Antonescu, {Cristina R.}",
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T2 - A Clinicopathologic and Molecular Analysis of 36 Cases with Comparison to Morphologic Spectrum and Clinical Behavior of Other Round Cell Sarcomas

AU - Kao, Yu-Chien

AU - Owosho, Adepitan A.

AU - Sung, Yun Shao

AU - Zhang, Lei

AU - Fujisawa, Yumi

AU - Lee, Jen Chieh

AU - Wexler, Leonard

AU - Argani, Pedram

AU - Swanson, David

AU - Dickson, Brendan C.

AU - Fletcher, Christopher D.M.

AU - Antonescu, Cristina R.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - BCOR-CCNB3 sarcoma (BCS) is a recently defined genetic entity among undifferentiated round cell sarcomas, which was initially classified as and treated similarly to the Ewing sarcoma (ES) family of tumors. In contrast to ES, BCS shows consistent BCOR overexpression, and preliminary evidence suggests that these tumors share morphologic features with other tumors harboring BCOR genetic alterations, including BCOR internal tandem duplication (ITD) and BCOR-MAML3. To further investigate the pathologic features, clinical behavior, and their relationship to other round cell sarcomas, we collected 36 molecularly confirmed BCSs for a detailed histologic and immunohistochemical analysis. Four of the cases were also analyzed by RNA sequencing (RNAseq). An additional case with BCOR overexpression but negative CCNB3 abnormality showed a novel KMT2D-BCOR fusion by targeted RNAseq. The patients ranged in age from 2 to 44 years old (mean and median, 15), with striking male predominance (M:F=31:5). The tumor locations were slightly more common in bone (n=20) than soft tissue (n=14), with rare visceral (kidney, n=2) involvement. Histologically, BCS showed a spectrum of round to spindle cells with variable cellularity, monomorphic nuclei and fine chromatin pattern, delicate capillary network, and varying amounts of myxoid or collagenous stroma. The morphologic features and immunoprofile showed considerable overlap with other round cell sarcomas with BCOR oncogenic upregulation, that is, BCOR-MAML3 and BCOR ITD. Follow-up available in 22 patients showed a 5-year overall survival of 72%, which was relatively similar to ES (79%, P=0.738) and significantly better than CIC-DUX4 sarcomas (43%, P=0.005) control groups. Local recurrences occurred in 6 patients and distant metastases (lung, soft tissue/bone, pancreas) in 4. Seven of 9 cases treated with an ES chemotherapy regimen with evaluable histologic response showed >60% necrosis in posttherapy resections. Unsupervised clustering by RNAseq data revealed that tumors with BCOR genetic alterations, including BCOR-CCNB3, BCOR-MAML3, and BCOR ITD, formed a tight genomic group distinct from ES and CIC-rearranged sarcomas.

AB - BCOR-CCNB3 sarcoma (BCS) is a recently defined genetic entity among undifferentiated round cell sarcomas, which was initially classified as and treated similarly to the Ewing sarcoma (ES) family of tumors. In contrast to ES, BCS shows consistent BCOR overexpression, and preliminary evidence suggests that these tumors share morphologic features with other tumors harboring BCOR genetic alterations, including BCOR internal tandem duplication (ITD) and BCOR-MAML3. To further investigate the pathologic features, clinical behavior, and their relationship to other round cell sarcomas, we collected 36 molecularly confirmed BCSs for a detailed histologic and immunohistochemical analysis. Four of the cases were also analyzed by RNA sequencing (RNAseq). An additional case with BCOR overexpression but negative CCNB3 abnormality showed a novel KMT2D-BCOR fusion by targeted RNAseq. The patients ranged in age from 2 to 44 years old (mean and median, 15), with striking male predominance (M:F=31:5). The tumor locations were slightly more common in bone (n=20) than soft tissue (n=14), with rare visceral (kidney, n=2) involvement. Histologically, BCS showed a spectrum of round to spindle cells with variable cellularity, monomorphic nuclei and fine chromatin pattern, delicate capillary network, and varying amounts of myxoid or collagenous stroma. The morphologic features and immunoprofile showed considerable overlap with other round cell sarcomas with BCOR oncogenic upregulation, that is, BCOR-MAML3 and BCOR ITD. Follow-up available in 22 patients showed a 5-year overall survival of 72%, which was relatively similar to ES (79%, P=0.738) and significantly better than CIC-DUX4 sarcomas (43%, P=0.005) control groups. Local recurrences occurred in 6 patients and distant metastases (lung, soft tissue/bone, pancreas) in 4. Seven of 9 cases treated with an ES chemotherapy regimen with evaluable histologic response showed >60% necrosis in posttherapy resections. Unsupervised clustering by RNAseq data revealed that tumors with BCOR genetic alterations, including BCOR-CCNB3, BCOR-MAML3, and BCOR ITD, formed a tight genomic group distinct from ES and CIC-rearranged sarcomas.

KW - BCOR

KW - CCNB3

KW - Ewing sarcoma

KW - fusions

KW - round cell sarcoma

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