NUTM2A fusions identified in aggressive infant sarcomas with gene expression and methylation patterns similar to CIC-rearranged sarcoma

Abstract CIC-rearranged sarcomas are newly defined undifferentiated soft tissue tumors with CIC-associated fusions, and dismal prognosis. CIC fusions activate PEA3 family genes, ETV1/4/5, leading to tumorigenesis and progression. We report two high-grade CNS sarcomas of unclear histological diagnosi...
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Autor*in:	Xu, Feng [verfasserIn] Viaene, Angela N. Ruiz, Jenny Schubert, Jeffrey Wu, Jinhua Chen, Jiani Cao, Kajia Fu, Weixuan Bagatell, Rochelle Fan, Zhiqian Long, Ariel Pagliaroli, Luca Zhong, Yiming Luo, Minjie Kreiger, Portia A. Surrey, Lea F. Wertheim, Gerald B. Cole, Kristina A. Li, Marilyn M. Santi, Mariarita Storm, Phillip B.

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	rearranged sarcoma -associated fusions Whole transcriptome sequencing

Anmerkung:	© The Author(s) 2022

Übergeordnetes Werk:	Enthalten in: Acta Neuropathologica Communications - London : Biomed Central, 2013, 10(2022), 1 vom: 14. Juli
Übergeordnetes Werk:	volume:10 ; year:2022 ; number:1 ; day:14 ; month:07

Links:	Volltext

DOI / URN:	10.1186/s40478-022-01401-z

Katalog-ID:	SPR050854151

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allfields	10.1186/s40478-022-01401-z doi (DE-627)SPR050854151 (SPR)s40478-022-01401-z-e DE-627 ger DE-627 rakwb eng Xu, Feng verfasserin aut Novel ATXN1/ATXN1L::NUTM2A fusions identified in aggressive infant sarcomas with gene expression and methylation patterns similar to CIC-rearranged sarcoma 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Abstract CIC-rearranged sarcomas are newly defined undifferentiated soft tissue tumors with CIC-associated fusions, and dismal prognosis. CIC fusions activate PEA3 family genes, ETV1/4/5, leading to tumorigenesis and progression. We report two high-grade CNS sarcomas of unclear histological diagnosis and one disseminated tumor of unknown origin with novel fusions and similar gene-expression/methylation patterns without CIC rearrangement. All three patients were infants with aggressive diseases, and two experienced rapid disease deterioration and death. Whole-transcriptome sequencing identified an ATXN1-NUTM2A fusion in the two CNS tumors and an ATXN1L-NUTM2A fusion in case 3. ETV1/4/5 and WT1 overexpression were observed in all three cases. Methylation analyses predicted CIC-rearranged sarcoma for all cases. Retrospective IHC staining on case 2 demonstrated ETV4 and WT1 overexpression. ATXN1 and ATXN1L interact with CIC forming a transcription repressor complex. We propose that ATXN1/ATXN1L-associated fusions disrupt their interaction with CIC and decrease the transcription repressor complex, leading to downstream PEA3 family gene overexpression. These three cases with novel ATXN1/ATXN1L-associated fusions and features of CIC-rearranged sarcomas may further expand the scope of “CIC-rearranged” sarcomas to include non-CIC rearrangements. Additional cases are needed to demonstrate if ATXN1/ATXN1L-NUTM2A fusions are associated with younger age and more aggressive diseases. rearranged sarcoma (dpeaa)DE-He213 -associated fusions (dpeaa)DE-He213 Whole transcriptome sequencing (dpeaa)DE-He213 Viaene, Angela N. aut Ruiz, Jenny aut Schubert, Jeffrey aut Wu, Jinhua aut Chen, Jiani aut Cao, Kajia aut Fu, Weixuan aut Bagatell, Rochelle aut Fan, Zhiqian aut Long, Ariel aut Pagliaroli, Luca aut Zhong, Yiming aut Luo, Minjie aut Kreiger, Portia A. aut Surrey, Lea F. aut Wertheim, Gerald B. aut Cole, Kristina A. aut Li, Marilyn M. (orcid)0000-0002-4253-2369 aut Santi, Mariarita aut Storm, Phillip B. aut Enthalten in Acta Neuropathologica Communications London : Biomed Central, 2013 10(2022), 1 vom: 14. Juli (DE-627)746066465 (DE-600)2715589-4 2051-5960 nnns volume:10 year:2022 number:1 day:14 month:07 https://dx.doi.org/10.1186/s40478-022-01401-z kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2022 1 14 07
spelling	10.1186/s40478-022-01401-z doi (DE-627)SPR050854151 (SPR)s40478-022-01401-z-e DE-627 ger DE-627 rakwb eng Xu, Feng verfasserin aut Novel ATXN1/ATXN1L::NUTM2A fusions identified in aggressive infant sarcomas with gene expression and methylation patterns similar to CIC-rearranged sarcoma 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Abstract CIC-rearranged sarcomas are newly defined undifferentiated soft tissue tumors with CIC-associated fusions, and dismal prognosis. CIC fusions activate PEA3 family genes, ETV1/4/5, leading to tumorigenesis and progression. We report two high-grade CNS sarcomas of unclear histological diagnosis and one disseminated tumor of unknown origin with novel fusions and similar gene-expression/methylation patterns without CIC rearrangement. All three patients were infants with aggressive diseases, and two experienced rapid disease deterioration and death. Whole-transcriptome sequencing identified an ATXN1-NUTM2A fusion in the two CNS tumors and an ATXN1L-NUTM2A fusion in case 3. ETV1/4/5 and WT1 overexpression were observed in all three cases. Methylation analyses predicted CIC-rearranged sarcoma for all cases. Retrospective IHC staining on case 2 demonstrated ETV4 and WT1 overexpression. ATXN1 and ATXN1L interact with CIC forming a transcription repressor complex. We propose that ATXN1/ATXN1L-associated fusions disrupt their interaction with CIC and decrease the transcription repressor complex, leading to downstream PEA3 family gene overexpression. These three cases with novel ATXN1/ATXN1L-associated fusions and features of CIC-rearranged sarcomas may further expand the scope of “CIC-rearranged” sarcomas to include non-CIC rearrangements. Additional cases are needed to demonstrate if ATXN1/ATXN1L-NUTM2A fusions are associated with younger age and more aggressive diseases. rearranged sarcoma (dpeaa)DE-He213 -associated fusions (dpeaa)DE-He213 Whole transcriptome sequencing (dpeaa)DE-He213 Viaene, Angela N. aut Ruiz, Jenny aut Schubert, Jeffrey aut Wu, Jinhua aut Chen, Jiani aut Cao, Kajia aut Fu, Weixuan aut Bagatell, Rochelle aut Fan, Zhiqian aut Long, Ariel aut Pagliaroli, Luca aut Zhong, Yiming aut Luo, Minjie aut Kreiger, Portia A. aut Surrey, Lea F. aut Wertheim, Gerald B. aut Cole, Kristina A. aut Li, Marilyn M. (orcid)0000-0002-4253-2369 aut Santi, Mariarita aut Storm, Phillip B. aut Enthalten in Acta Neuropathologica Communications London : Biomed Central, 2013 10(2022), 1 vom: 14. Juli (DE-627)746066465 (DE-600)2715589-4 2051-5960 nnns volume:10 year:2022 number:1 day:14 month:07 https://dx.doi.org/10.1186/s40478-022-01401-z kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2022 1 14 07
allfields_unstemmed	10.1186/s40478-022-01401-z doi (DE-627)SPR050854151 (SPR)s40478-022-01401-z-e DE-627 ger DE-627 rakwb eng Xu, Feng verfasserin aut Novel ATXN1/ATXN1L::NUTM2A fusions identified in aggressive infant sarcomas with gene expression and methylation patterns similar to CIC-rearranged sarcoma 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Abstract CIC-rearranged sarcomas are newly defined undifferentiated soft tissue tumors with CIC-associated fusions, and dismal prognosis. CIC fusions activate PEA3 family genes, ETV1/4/5, leading to tumorigenesis and progression. We report two high-grade CNS sarcomas of unclear histological diagnosis and one disseminated tumor of unknown origin with novel fusions and similar gene-expression/methylation patterns without CIC rearrangement. All three patients were infants with aggressive diseases, and two experienced rapid disease deterioration and death. Whole-transcriptome sequencing identified an ATXN1-NUTM2A fusion in the two CNS tumors and an ATXN1L-NUTM2A fusion in case 3. ETV1/4/5 and WT1 overexpression were observed in all three cases. Methylation analyses predicted CIC-rearranged sarcoma for all cases. Retrospective IHC staining on case 2 demonstrated ETV4 and WT1 overexpression. ATXN1 and ATXN1L interact with CIC forming a transcription repressor complex. We propose that ATXN1/ATXN1L-associated fusions disrupt their interaction with CIC and decrease the transcription repressor complex, leading to downstream PEA3 family gene overexpression. These three cases with novel ATXN1/ATXN1L-associated fusions and features of CIC-rearranged sarcomas may further expand the scope of “CIC-rearranged” sarcomas to include non-CIC rearrangements. Additional cases are needed to demonstrate if ATXN1/ATXN1L-NUTM2A fusions are associated with younger age and more aggressive diseases. rearranged sarcoma (dpeaa)DE-He213 -associated fusions (dpeaa)DE-He213 Whole transcriptome sequencing (dpeaa)DE-He213 Viaene, Angela N. aut Ruiz, Jenny aut Schubert, Jeffrey aut Wu, Jinhua aut Chen, Jiani aut Cao, Kajia aut Fu, Weixuan aut Bagatell, Rochelle aut Fan, Zhiqian aut Long, Ariel aut Pagliaroli, Luca aut Zhong, Yiming aut Luo, Minjie aut Kreiger, Portia A. aut Surrey, Lea F. aut Wertheim, Gerald B. aut Cole, Kristina A. aut Li, Marilyn M. (orcid)0000-0002-4253-2369 aut Santi, Mariarita aut Storm, Phillip B. aut Enthalten in Acta Neuropathologica Communications London : Biomed Central, 2013 10(2022), 1 vom: 14. Juli (DE-627)746066465 (DE-600)2715589-4 2051-5960 nnns volume:10 year:2022 number:1 day:14 month:07 https://dx.doi.org/10.1186/s40478-022-01401-z kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2022 1 14 07
allfieldsGer	10.1186/s40478-022-01401-z doi (DE-627)SPR050854151 (SPR)s40478-022-01401-z-e DE-627 ger DE-627 rakwb eng Xu, Feng verfasserin aut Novel ATXN1/ATXN1L::NUTM2A fusions identified in aggressive infant sarcomas with gene expression and methylation patterns similar to CIC-rearranged sarcoma 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Abstract CIC-rearranged sarcomas are newly defined undifferentiated soft tissue tumors with CIC-associated fusions, and dismal prognosis. CIC fusions activate PEA3 family genes, ETV1/4/5, leading to tumorigenesis and progression. We report two high-grade CNS sarcomas of unclear histological diagnosis and one disseminated tumor of unknown origin with novel fusions and similar gene-expression/methylation patterns without CIC rearrangement. All three patients were infants with aggressive diseases, and two experienced rapid disease deterioration and death. Whole-transcriptome sequencing identified an ATXN1-NUTM2A fusion in the two CNS tumors and an ATXN1L-NUTM2A fusion in case 3. ETV1/4/5 and WT1 overexpression were observed in all three cases. Methylation analyses predicted CIC-rearranged sarcoma for all cases. Retrospective IHC staining on case 2 demonstrated ETV4 and WT1 overexpression. ATXN1 and ATXN1L interact with CIC forming a transcription repressor complex. We propose that ATXN1/ATXN1L-associated fusions disrupt their interaction with CIC and decrease the transcription repressor complex, leading to downstream PEA3 family gene overexpression. These three cases with novel ATXN1/ATXN1L-associated fusions and features of CIC-rearranged sarcomas may further expand the scope of “CIC-rearranged” sarcomas to include non-CIC rearrangements. Additional cases are needed to demonstrate if ATXN1/ATXN1L-NUTM2A fusions are associated with younger age and more aggressive diseases. rearranged sarcoma (dpeaa)DE-He213 -associated fusions (dpeaa)DE-He213 Whole transcriptome sequencing (dpeaa)DE-He213 Viaene, Angela N. aut Ruiz, Jenny aut Schubert, Jeffrey aut Wu, Jinhua aut Chen, Jiani aut Cao, Kajia aut Fu, Weixuan aut Bagatell, Rochelle aut Fan, Zhiqian aut Long, Ariel aut Pagliaroli, Luca aut Zhong, Yiming aut Luo, Minjie aut Kreiger, Portia A. aut Surrey, Lea F. aut Wertheim, Gerald B. aut Cole, Kristina A. aut Li, Marilyn M. (orcid)0000-0002-4253-2369 aut Santi, Mariarita aut Storm, Phillip B. aut Enthalten in Acta Neuropathologica Communications London : Biomed Central, 2013 10(2022), 1 vom: 14. Juli (DE-627)746066465 (DE-600)2715589-4 2051-5960 nnns volume:10 year:2022 number:1 day:14 month:07 https://dx.doi.org/10.1186/s40478-022-01401-z kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2022 1 14 07
allfieldsSound	10.1186/s40478-022-01401-z doi (DE-627)SPR050854151 (SPR)s40478-022-01401-z-e DE-627 ger DE-627 rakwb eng Xu, Feng verfasserin aut Novel ATXN1/ATXN1L::NUTM2A fusions identified in aggressive infant sarcomas with gene expression and methylation patterns similar to CIC-rearranged sarcoma 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Abstract CIC-rearranged sarcomas are newly defined undifferentiated soft tissue tumors with CIC-associated fusions, and dismal prognosis. CIC fusions activate PEA3 family genes, ETV1/4/5, leading to tumorigenesis and progression. We report two high-grade CNS sarcomas of unclear histological diagnosis and one disseminated tumor of unknown origin with novel fusions and similar gene-expression/methylation patterns without CIC rearrangement. All three patients were infants with aggressive diseases, and two experienced rapid disease deterioration and death. Whole-transcriptome sequencing identified an ATXN1-NUTM2A fusion in the two CNS tumors and an ATXN1L-NUTM2A fusion in case 3. ETV1/4/5 and WT1 overexpression were observed in all three cases. Methylation analyses predicted CIC-rearranged sarcoma for all cases. Retrospective IHC staining on case 2 demonstrated ETV4 and WT1 overexpression. ATXN1 and ATXN1L interact with CIC forming a transcription repressor complex. We propose that ATXN1/ATXN1L-associated fusions disrupt their interaction with CIC and decrease the transcription repressor complex, leading to downstream PEA3 family gene overexpression. These three cases with novel ATXN1/ATXN1L-associated fusions and features of CIC-rearranged sarcomas may further expand the scope of “CIC-rearranged” sarcomas to include non-CIC rearrangements. Additional cases are needed to demonstrate if ATXN1/ATXN1L-NUTM2A fusions are associated with younger age and more aggressive diseases. rearranged sarcoma (dpeaa)DE-He213 -associated fusions (dpeaa)DE-He213 Whole transcriptome sequencing (dpeaa)DE-He213 Viaene, Angela N. aut Ruiz, Jenny aut Schubert, Jeffrey aut Wu, Jinhua aut Chen, Jiani aut Cao, Kajia aut Fu, Weixuan aut Bagatell, Rochelle aut Fan, Zhiqian aut Long, Ariel aut Pagliaroli, Luca aut Zhong, Yiming aut Luo, Minjie aut Kreiger, Portia A. aut Surrey, Lea F. aut Wertheim, Gerald B. aut Cole, Kristina A. aut Li, Marilyn M. (orcid)0000-0002-4253-2369 aut Santi, Mariarita aut Storm, Phillip B. aut Enthalten in Acta Neuropathologica Communications London : Biomed Central, 2013 10(2022), 1 vom: 14. Juli (DE-627)746066465 (DE-600)2715589-4 2051-5960 nnns volume:10 year:2022 number:1 day:14 month:07 https://dx.doi.org/10.1186/s40478-022-01401-z kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2022 1 14 07
language	English
source	Enthalten in Acta Neuropathologica Communications 10(2022), 1 vom: 14. Juli volume:10 year:2022 number:1 day:14 month:07
sourceStr	Enthalten in Acta Neuropathologica Communications 10(2022), 1 vom: 14. Juli volume:10 year:2022 number:1 day:14 month:07
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	rearranged sarcoma -associated fusions Whole transcriptome sequencing
isfreeaccess_bool	true
container_title	Acta Neuropathologica Communications
authorswithroles_txt_mv	Xu, Feng @@aut@@ Viaene, Angela N. @@aut@@ Ruiz, Jenny @@aut@@ Schubert, Jeffrey @@aut@@ Wu, Jinhua @@aut@@ Chen, Jiani @@aut@@ Cao, Kajia @@aut@@ Fu, Weixuan @@aut@@ Bagatell, Rochelle @@aut@@ Fan, Zhiqian @@aut@@ Long, Ariel @@aut@@ Pagliaroli, Luca @@aut@@ Zhong, Yiming @@aut@@ Luo, Minjie @@aut@@ Kreiger, Portia A. @@aut@@ Surrey, Lea F. @@aut@@ Wertheim, Gerald B. @@aut@@ Cole, Kristina A. @@aut@@ Li, Marilyn M. @@aut@@ Santi, Mariarita @@aut@@ Storm, Phillip B. @@aut@@
publishDateDaySort_date	2022-07-14T00:00:00Z
hierarchy_top_id	746066465
id	SPR050854151
language_de	englisch
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author	Xu, Feng
spellingShingle	Xu, Feng misc rearranged sarcoma misc -associated fusions misc Whole transcriptome sequencing Novel ATXN1/ATXN1L::NUTM2A fusions identified in aggressive infant sarcomas with gene expression and methylation patterns similar to CIC-rearranged sarcoma
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topic_title	Novel ATXN1/ATXN1L::NUTM2A fusions identified in aggressive infant sarcomas with gene expression and methylation patterns similar to CIC-rearranged sarcoma rearranged sarcoma (dpeaa)DE-He213 -associated fusions (dpeaa)DE-He213 Whole transcriptome sequencing (dpeaa)DE-He213
topic	misc rearranged sarcoma misc -associated fusions misc Whole transcriptome sequencing
topic_unstemmed	misc rearranged sarcoma misc -associated fusions misc Whole transcriptome sequencing
topic_browse	misc rearranged sarcoma misc -associated fusions misc Whole transcriptome sequencing
format_facet	Elektronische Aufsätze Aufsätze Elektronische Ressource
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title	Novel ATXN1/ATXN1L::NUTM2A fusions identified in aggressive infant sarcomas with gene expression and methylation patterns similar to CIC-rearranged sarcoma
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title_full	Novel ATXN1/ATXN1L::NUTM2A fusions identified in aggressive infant sarcomas with gene expression and methylation patterns similar to CIC-rearranged sarcoma
author_sort	Xu, Feng
journal	Acta Neuropathologica Communications
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author_browse	Xu, Feng Viaene, Angela N. Ruiz, Jenny Schubert, Jeffrey Wu, Jinhua Chen, Jiani Cao, Kajia Fu, Weixuan Bagatell, Rochelle Fan, Zhiqian Long, Ariel Pagliaroli, Luca Zhong, Yiming Luo, Minjie Kreiger, Portia A. Surrey, Lea F. Wertheim, Gerald B. Cole, Kristina A. Li, Marilyn M. Santi, Mariarita Storm, Phillip B.
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author-letter	Xu, Feng
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title_sort	novel atxn1/atxn1l::nutm2a fusions identified in aggressive infant sarcomas with gene expression and methylation patterns similar to cic-rearranged sarcoma
title_auth	Novel ATXN1/ATXN1L::NUTM2A fusions identified in aggressive infant sarcomas with gene expression and methylation patterns similar to CIC-rearranged sarcoma
abstract	Abstract CIC-rearranged sarcomas are newly defined undifferentiated soft tissue tumors with CIC-associated fusions, and dismal prognosis. CIC fusions activate PEA3 family genes, ETV1/4/5, leading to tumorigenesis and progression. We report two high-grade CNS sarcomas of unclear histological diagnosis and one disseminated tumor of unknown origin with novel fusions and similar gene-expression/methylation patterns without CIC rearrangement. All three patients were infants with aggressive diseases, and two experienced rapid disease deterioration and death. Whole-transcriptome sequencing identified an ATXN1-NUTM2A fusion in the two CNS tumors and an ATXN1L-NUTM2A fusion in case 3. ETV1/4/5 and WT1 overexpression were observed in all three cases. Methylation analyses predicted CIC-rearranged sarcoma for all cases. Retrospective IHC staining on case 2 demonstrated ETV4 and WT1 overexpression. ATXN1 and ATXN1L interact with CIC forming a transcription repressor complex. We propose that ATXN1/ATXN1L-associated fusions disrupt their interaction with CIC and decrease the transcription repressor complex, leading to downstream PEA3 family gene overexpression. These three cases with novel ATXN1/ATXN1L-associated fusions and features of CIC-rearranged sarcomas may further expand the scope of “CIC-rearranged” sarcomas to include non-CIC rearrangements. Additional cases are needed to demonstrate if ATXN1/ATXN1L-NUTM2A fusions are associated with younger age and more aggressive diseases. © The Author(s) 2022
abstractGer	Abstract CIC-rearranged sarcomas are newly defined undifferentiated soft tissue tumors with CIC-associated fusions, and dismal prognosis. CIC fusions activate PEA3 family genes, ETV1/4/5, leading to tumorigenesis and progression. We report two high-grade CNS sarcomas of unclear histological diagnosis and one disseminated tumor of unknown origin with novel fusions and similar gene-expression/methylation patterns without CIC rearrangement. All three patients were infants with aggressive diseases, and two experienced rapid disease deterioration and death. Whole-transcriptome sequencing identified an ATXN1-NUTM2A fusion in the two CNS tumors and an ATXN1L-NUTM2A fusion in case 3. ETV1/4/5 and WT1 overexpression were observed in all three cases. Methylation analyses predicted CIC-rearranged sarcoma for all cases. Retrospective IHC staining on case 2 demonstrated ETV4 and WT1 overexpression. ATXN1 and ATXN1L interact with CIC forming a transcription repressor complex. We propose that ATXN1/ATXN1L-associated fusions disrupt their interaction with CIC and decrease the transcription repressor complex, leading to downstream PEA3 family gene overexpression. These three cases with novel ATXN1/ATXN1L-associated fusions and features of CIC-rearranged sarcomas may further expand the scope of “CIC-rearranged” sarcomas to include non-CIC rearrangements. Additional cases are needed to demonstrate if ATXN1/ATXN1L-NUTM2A fusions are associated with younger age and more aggressive diseases. © The Author(s) 2022
abstract_unstemmed	Abstract CIC-rearranged sarcomas are newly defined undifferentiated soft tissue tumors with CIC-associated fusions, and dismal prognosis. CIC fusions activate PEA3 family genes, ETV1/4/5, leading to tumorigenesis and progression. We report two high-grade CNS sarcomas of unclear histological diagnosis and one disseminated tumor of unknown origin with novel fusions and similar gene-expression/methylation patterns without CIC rearrangement. All three patients were infants with aggressive diseases, and two experienced rapid disease deterioration and death. Whole-transcriptome sequencing identified an ATXN1-NUTM2A fusion in the two CNS tumors and an ATXN1L-NUTM2A fusion in case 3. ETV1/4/5 and WT1 overexpression were observed in all three cases. Methylation analyses predicted CIC-rearranged sarcoma for all cases. Retrospective IHC staining on case 2 demonstrated ETV4 and WT1 overexpression. ATXN1 and ATXN1L interact with CIC forming a transcription repressor complex. We propose that ATXN1/ATXN1L-associated fusions disrupt their interaction with CIC and decrease the transcription repressor complex, leading to downstream PEA3 family gene overexpression. These three cases with novel ATXN1/ATXN1L-associated fusions and features of CIC-rearranged sarcomas may further expand the scope of “CIC-rearranged” sarcomas to include non-CIC rearrangements. Additional cases are needed to demonstrate if ATXN1/ATXN1L-NUTM2A fusions are associated with younger age and more aggressive diseases. © The Author(s) 2022
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title_short	Novel ATXN1/ATXN1L::NUTM2A fusions identified in aggressive infant sarcomas with gene expression and methylation patterns similar to CIC-rearranged sarcoma
url	https://dx.doi.org/10.1186/s40478-022-01401-z
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author2	Viaene, Angela N. Ruiz, Jenny Schubert, Jeffrey Wu, Jinhua Chen, Jiani Cao, Kajia Fu, Weixuan Bagatell, Rochelle Fan, Zhiqian Long, Ariel Pagliaroli, Luca Zhong, Yiming Luo, Minjie Kreiger, Portia A. Surrey, Lea F. Wertheim, Gerald B. Cole, Kristina A. Li, Marilyn M. Santi, Mariarita Storm, Phillip B.
author2Str	Viaene, Angela N. Ruiz, Jenny Schubert, Jeffrey Wu, Jinhua Chen, Jiani Cao, Kajia Fu, Weixuan Bagatell, Rochelle Fan, Zhiqian Long, Ariel Pagliaroli, Luca Zhong, Yiming Luo, Minjie Kreiger, Portia A. Surrey, Lea F. Wertheim, Gerald B. Cole, Kristina A. Li, Marilyn M. Santi, Mariarita Storm, Phillip B.
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NUTM2A fusions identified in aggressive infant sarcomas with gene expression and methylation patterns similar to CIC-rearranged sarcoma

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