Allele-specific expression reveals genes with recurrent cis-regulatory alterations in high-risk neuroblastoma

Background Neuroblastoma is a pediatric malignancy with a high frequency of metastatic disease at initial diagnosis. Neuroblastoma tumors have few recurrent protein-coding mutations but contain extensive somatic copy number alterations (SCNAs) suggesting that mutations that alter gene dosage are imp...
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Autor*in:	Sen, Arko [verfasserIn] Huo, Yuchen Elster, Jennifer Zage, Peter E. McVicker, Graham

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Anmerkung:	© The Author(s) 2022

Übergeordnetes Werk:	Enthalten in: Genome biology - London : BioMed Central, 2000, 23(2022), 1 vom: 04. März
Übergeordnetes Werk:	volume:23 ; year:2022 ; number:1 ; day:04 ; month:03

Links:	Volltext

DOI / URN:	10.1186/s13059-022-02640-y

Katalog-ID:	SPR050529889

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520			\|a Background Neuroblastoma is a pediatric malignancy with a high frequency of metastatic disease at initial diagnosis. Neuroblastoma tumors have few recurrent protein-coding mutations but contain extensive somatic copy number alterations (SCNAs) suggesting that mutations that alter gene dosage are important drivers of tumorigenesis. Here, we analyze allele-specific expression in 96 high-risk neuroblastoma tumors to discover genes impacted by cis-acting mutations that alter dosage. Results We identify 1043 genes with recurrent, neuroblastoma-specific allele-specific expression. While most of these genes lie within common SCNA regions, many of them exhibit allele-specific expression in copy neutral samples and these samples are enriched for mutations that are predicted to cause nonsense-mediated decay. Thus, both SCNA and non-SCNA mutations frequently alter gene expression in neuroblastoma. We focus on genes with neuroblastoma-specific allele-specific expression in the absence of SCNAs and find 26 such genes that have reduced expression in stage 4 disease. At least two of these genes have evidence for tumor suppressor activity including the transcription factor TFAP2B and the protein tyrosine phosphatase PTPRH. Conclusions In summary, our allele-specific expression analysis discovers genes that are recurrently dysregulated by both large SCNAs and other cis-acting mutations in high-risk neuroblastoma.
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allfields	10.1186/s13059-022-02640-y doi (DE-627)SPR050529889 (SPR)s13059-022-02640-y-e DE-627 ger DE-627 rakwb eng Sen, Arko verfasserin aut Allele-specific expression reveals genes with recurrent cis-regulatory alterations in high-risk neuroblastoma 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Neuroblastoma is a pediatric malignancy with a high frequency of metastatic disease at initial diagnosis. Neuroblastoma tumors have few recurrent protein-coding mutations but contain extensive somatic copy number alterations (SCNAs) suggesting that mutations that alter gene dosage are important drivers of tumorigenesis. Here, we analyze allele-specific expression in 96 high-risk neuroblastoma tumors to discover genes impacted by cis-acting mutations that alter dosage. Results We identify 1043 genes with recurrent, neuroblastoma-specific allele-specific expression. While most of these genes lie within common SCNA regions, many of them exhibit allele-specific expression in copy neutral samples and these samples are enriched for mutations that are predicted to cause nonsense-mediated decay. Thus, both SCNA and non-SCNA mutations frequently alter gene expression in neuroblastoma. We focus on genes with neuroblastoma-specific allele-specific expression in the absence of SCNAs and find 26 such genes that have reduced expression in stage 4 disease. At least two of these genes have evidence for tumor suppressor activity including the transcription factor TFAP2B and the protein tyrosine phosphatase PTPRH. Conclusions In summary, our allele-specific expression analysis discovers genes that are recurrently dysregulated by both large SCNAs and other cis-acting mutations in high-risk neuroblastoma. Huo, Yuchen aut Elster, Jennifer aut Zage, Peter E. aut McVicker, Graham (orcid)0000-0003-0991-0951 aut Enthalten in Genome biology London : BioMed Central, 2000 23(2022), 1 vom: 04. März (DE-627)326173617 (DE-600)2040529-7 1474-760X nnns volume:23 year:2022 number:1 day:04 month:03 https://dx.doi.org/10.1186/s13059-022-02640-y 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_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 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 23 2022 1 04 03
spelling	10.1186/s13059-022-02640-y doi (DE-627)SPR050529889 (SPR)s13059-022-02640-y-e DE-627 ger DE-627 rakwb eng Sen, Arko verfasserin aut Allele-specific expression reveals genes with recurrent cis-regulatory alterations in high-risk neuroblastoma 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Neuroblastoma is a pediatric malignancy with a high frequency of metastatic disease at initial diagnosis. Neuroblastoma tumors have few recurrent protein-coding mutations but contain extensive somatic copy number alterations (SCNAs) suggesting that mutations that alter gene dosage are important drivers of tumorigenesis. Here, we analyze allele-specific expression in 96 high-risk neuroblastoma tumors to discover genes impacted by cis-acting mutations that alter dosage. Results We identify 1043 genes with recurrent, neuroblastoma-specific allele-specific expression. While most of these genes lie within common SCNA regions, many of them exhibit allele-specific expression in copy neutral samples and these samples are enriched for mutations that are predicted to cause nonsense-mediated decay. Thus, both SCNA and non-SCNA mutations frequently alter gene expression in neuroblastoma. We focus on genes with neuroblastoma-specific allele-specific expression in the absence of SCNAs and find 26 such genes that have reduced expression in stage 4 disease. At least two of these genes have evidence for tumor suppressor activity including the transcription factor TFAP2B and the protein tyrosine phosphatase PTPRH. Conclusions In summary, our allele-specific expression analysis discovers genes that are recurrently dysregulated by both large SCNAs and other cis-acting mutations in high-risk neuroblastoma. Huo, Yuchen aut Elster, Jennifer aut Zage, Peter E. aut McVicker, Graham (orcid)0000-0003-0991-0951 aut Enthalten in Genome biology London : BioMed Central, 2000 23(2022), 1 vom: 04. März (DE-627)326173617 (DE-600)2040529-7 1474-760X nnns volume:23 year:2022 number:1 day:04 month:03 https://dx.doi.org/10.1186/s13059-022-02640-y 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_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 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 23 2022 1 04 03
allfields_unstemmed	10.1186/s13059-022-02640-y doi (DE-627)SPR050529889 (SPR)s13059-022-02640-y-e DE-627 ger DE-627 rakwb eng Sen, Arko verfasserin aut Allele-specific expression reveals genes with recurrent cis-regulatory alterations in high-risk neuroblastoma 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Neuroblastoma is a pediatric malignancy with a high frequency of metastatic disease at initial diagnosis. Neuroblastoma tumors have few recurrent protein-coding mutations but contain extensive somatic copy number alterations (SCNAs) suggesting that mutations that alter gene dosage are important drivers of tumorigenesis. Here, we analyze allele-specific expression in 96 high-risk neuroblastoma tumors to discover genes impacted by cis-acting mutations that alter dosage. Results We identify 1043 genes with recurrent, neuroblastoma-specific allele-specific expression. While most of these genes lie within common SCNA regions, many of them exhibit allele-specific expression in copy neutral samples and these samples are enriched for mutations that are predicted to cause nonsense-mediated decay. Thus, both SCNA and non-SCNA mutations frequently alter gene expression in neuroblastoma. We focus on genes with neuroblastoma-specific allele-specific expression in the absence of SCNAs and find 26 such genes that have reduced expression in stage 4 disease. At least two of these genes have evidence for tumor suppressor activity including the transcription factor TFAP2B and the protein tyrosine phosphatase PTPRH. Conclusions In summary, our allele-specific expression analysis discovers genes that are recurrently dysregulated by both large SCNAs and other cis-acting mutations in high-risk neuroblastoma. Huo, Yuchen aut Elster, Jennifer aut Zage, Peter E. aut McVicker, Graham (orcid)0000-0003-0991-0951 aut Enthalten in Genome biology London : BioMed Central, 2000 23(2022), 1 vom: 04. März (DE-627)326173617 (DE-600)2040529-7 1474-760X nnns volume:23 year:2022 number:1 day:04 month:03 https://dx.doi.org/10.1186/s13059-022-02640-y 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_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 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 23 2022 1 04 03
allfieldsGer	10.1186/s13059-022-02640-y doi (DE-627)SPR050529889 (SPR)s13059-022-02640-y-e DE-627 ger DE-627 rakwb eng Sen, Arko verfasserin aut Allele-specific expression reveals genes with recurrent cis-regulatory alterations in high-risk neuroblastoma 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Neuroblastoma is a pediatric malignancy with a high frequency of metastatic disease at initial diagnosis. Neuroblastoma tumors have few recurrent protein-coding mutations but contain extensive somatic copy number alterations (SCNAs) suggesting that mutations that alter gene dosage are important drivers of tumorigenesis. Here, we analyze allele-specific expression in 96 high-risk neuroblastoma tumors to discover genes impacted by cis-acting mutations that alter dosage. Results We identify 1043 genes with recurrent, neuroblastoma-specific allele-specific expression. While most of these genes lie within common SCNA regions, many of them exhibit allele-specific expression in copy neutral samples and these samples are enriched for mutations that are predicted to cause nonsense-mediated decay. Thus, both SCNA and non-SCNA mutations frequently alter gene expression in neuroblastoma. We focus on genes with neuroblastoma-specific allele-specific expression in the absence of SCNAs and find 26 such genes that have reduced expression in stage 4 disease. At least two of these genes have evidence for tumor suppressor activity including the transcription factor TFAP2B and the protein tyrosine phosphatase PTPRH. Conclusions In summary, our allele-specific expression analysis discovers genes that are recurrently dysregulated by both large SCNAs and other cis-acting mutations in high-risk neuroblastoma. Huo, Yuchen aut Elster, Jennifer aut Zage, Peter E. aut McVicker, Graham (orcid)0000-0003-0991-0951 aut Enthalten in Genome biology London : BioMed Central, 2000 23(2022), 1 vom: 04. März (DE-627)326173617 (DE-600)2040529-7 1474-760X nnns volume:23 year:2022 number:1 day:04 month:03 https://dx.doi.org/10.1186/s13059-022-02640-y 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_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 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 23 2022 1 04 03
allfieldsSound	10.1186/s13059-022-02640-y doi (DE-627)SPR050529889 (SPR)s13059-022-02640-y-e DE-627 ger DE-627 rakwb eng Sen, Arko verfasserin aut Allele-specific expression reveals genes with recurrent cis-regulatory alterations in high-risk neuroblastoma 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Neuroblastoma is a pediatric malignancy with a high frequency of metastatic disease at initial diagnosis. Neuroblastoma tumors have few recurrent protein-coding mutations but contain extensive somatic copy number alterations (SCNAs) suggesting that mutations that alter gene dosage are important drivers of tumorigenesis. Here, we analyze allele-specific expression in 96 high-risk neuroblastoma tumors to discover genes impacted by cis-acting mutations that alter dosage. Results We identify 1043 genes with recurrent, neuroblastoma-specific allele-specific expression. While most of these genes lie within common SCNA regions, many of them exhibit allele-specific expression in copy neutral samples and these samples are enriched for mutations that are predicted to cause nonsense-mediated decay. Thus, both SCNA and non-SCNA mutations frequently alter gene expression in neuroblastoma. We focus on genes with neuroblastoma-specific allele-specific expression in the absence of SCNAs and find 26 such genes that have reduced expression in stage 4 disease. At least two of these genes have evidence for tumor suppressor activity including the transcription factor TFAP2B and the protein tyrosine phosphatase PTPRH. Conclusions In summary, our allele-specific expression analysis discovers genes that are recurrently dysregulated by both large SCNAs and other cis-acting mutations in high-risk neuroblastoma. Huo, Yuchen aut Elster, Jennifer aut Zage, Peter E. aut McVicker, Graham (orcid)0000-0003-0991-0951 aut Enthalten in Genome biology London : BioMed Central, 2000 23(2022), 1 vom: 04. März (DE-627)326173617 (DE-600)2040529-7 1474-760X nnns volume:23 year:2022 number:1 day:04 month:03 https://dx.doi.org/10.1186/s13059-022-02640-y 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_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 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 23 2022 1 04 03
language	English
source	Enthalten in Genome biology 23(2022), 1 vom: 04. März volume:23 year:2022 number:1 day:04 month:03
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Neuroblastoma tumors have few recurrent protein-coding mutations but contain extensive somatic copy number alterations (SCNAs) suggesting that mutations that alter gene dosage are important drivers of tumorigenesis. Here, we analyze allele-specific expression in 96 high-risk neuroblastoma tumors to discover genes impacted by cis-acting mutations that alter dosage. Results We identify 1043 genes with recurrent, neuroblastoma-specific allele-specific expression. While most of these genes lie within common SCNA regions, many of them exhibit allele-specific expression in copy neutral samples and these samples are enriched for mutations that are predicted to cause nonsense-mediated decay. Thus, both SCNA and non-SCNA mutations frequently alter gene expression in neuroblastoma. We focus on genes with neuroblastoma-specific allele-specific expression in the absence of SCNAs and find 26 such genes that have reduced expression in stage 4 disease. 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author	Sen, Arko
spellingShingle	Sen, Arko Allele-specific expression reveals genes with recurrent cis-regulatory alterations in high-risk neuroblastoma
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topic_title	Allele-specific expression reveals genes with recurrent cis-regulatory alterations in high-risk neuroblastoma
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title	Allele-specific expression reveals genes with recurrent cis-regulatory alterations in high-risk neuroblastoma
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title_full	Allele-specific expression reveals genes with recurrent cis-regulatory alterations in high-risk neuroblastoma
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author_browse	Sen, Arko Huo, Yuchen Elster, Jennifer Zage, Peter E. McVicker, Graham
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title_sort	allele-specific expression reveals genes with recurrent cis-regulatory alterations in high-risk neuroblastoma
title_auth	Allele-specific expression reveals genes with recurrent cis-regulatory alterations in high-risk neuroblastoma
abstract	Background Neuroblastoma is a pediatric malignancy with a high frequency of metastatic disease at initial diagnosis. Neuroblastoma tumors have few recurrent protein-coding mutations but contain extensive somatic copy number alterations (SCNAs) suggesting that mutations that alter gene dosage are important drivers of tumorigenesis. Here, we analyze allele-specific expression in 96 high-risk neuroblastoma tumors to discover genes impacted by cis-acting mutations that alter dosage. Results We identify 1043 genes with recurrent, neuroblastoma-specific allele-specific expression. While most of these genes lie within common SCNA regions, many of them exhibit allele-specific expression in copy neutral samples and these samples are enriched for mutations that are predicted to cause nonsense-mediated decay. Thus, both SCNA and non-SCNA mutations frequently alter gene expression in neuroblastoma. We focus on genes with neuroblastoma-specific allele-specific expression in the absence of SCNAs and find 26 such genes that have reduced expression in stage 4 disease. At least two of these genes have evidence for tumor suppressor activity including the transcription factor TFAP2B and the protein tyrosine phosphatase PTPRH. Conclusions In summary, our allele-specific expression analysis discovers genes that are recurrently dysregulated by both large SCNAs and other cis-acting mutations in high-risk neuroblastoma. © The Author(s) 2022
abstractGer	Background Neuroblastoma is a pediatric malignancy with a high frequency of metastatic disease at initial diagnosis. Neuroblastoma tumors have few recurrent protein-coding mutations but contain extensive somatic copy number alterations (SCNAs) suggesting that mutations that alter gene dosage are important drivers of tumorigenesis. Here, we analyze allele-specific expression in 96 high-risk neuroblastoma tumors to discover genes impacted by cis-acting mutations that alter dosage. Results We identify 1043 genes with recurrent, neuroblastoma-specific allele-specific expression. While most of these genes lie within common SCNA regions, many of them exhibit allele-specific expression in copy neutral samples and these samples are enriched for mutations that are predicted to cause nonsense-mediated decay. Thus, both SCNA and non-SCNA mutations frequently alter gene expression in neuroblastoma. We focus on genes with neuroblastoma-specific allele-specific expression in the absence of SCNAs and find 26 such genes that have reduced expression in stage 4 disease. At least two of these genes have evidence for tumor suppressor activity including the transcription factor TFAP2B and the protein tyrosine phosphatase PTPRH. Conclusions In summary, our allele-specific expression analysis discovers genes that are recurrently dysregulated by both large SCNAs and other cis-acting mutations in high-risk neuroblastoma. © The Author(s) 2022
abstract_unstemmed	Background Neuroblastoma is a pediatric malignancy with a high frequency of metastatic disease at initial diagnosis. Neuroblastoma tumors have few recurrent protein-coding mutations but contain extensive somatic copy number alterations (SCNAs) suggesting that mutations that alter gene dosage are important drivers of tumorigenesis. Here, we analyze allele-specific expression in 96 high-risk neuroblastoma tumors to discover genes impacted by cis-acting mutations that alter dosage. Results We identify 1043 genes with recurrent, neuroblastoma-specific allele-specific expression. While most of these genes lie within common SCNA regions, many of them exhibit allele-specific expression in copy neutral samples and these samples are enriched for mutations that are predicted to cause nonsense-mediated decay. Thus, both SCNA and non-SCNA mutations frequently alter gene expression in neuroblastoma. We focus on genes with neuroblastoma-specific allele-specific expression in the absence of SCNAs and find 26 such genes that have reduced expression in stage 4 disease. At least two of these genes have evidence for tumor suppressor activity including the transcription factor TFAP2B and the protein tyrosine phosphatase PTPRH. Conclusions In summary, our allele-specific expression analysis discovers genes that are recurrently dysregulated by both large SCNAs and other cis-acting mutations in high-risk neuroblastoma. © The Author(s) 2022
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title_short	Allele-specific expression reveals genes with recurrent cis-regulatory alterations in high-risk neuroblastoma
url	https://dx.doi.org/10.1186/s13059-022-02640-y
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author2	Huo, Yuchen Elster, Jennifer Zage, Peter E. McVicker, Graham
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