Expression and Mutation Patterns of PBRM1, BAP1 and SETD2 Mirror Specific Evolutionary Subtypes in Clear Cell Renal Cell Carcinoma1
Bi-allelic inactivation of the VHL gene on chromosome 3p is the characteristic feature in most clear cell renal cell carcinomas (ccRCC). Frequent gene alterations were also identified in SETD2 , BAP1 and PBRM1, all of which are situated on chromosome 3p and encode histone/chromatin regulators. The r...
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| Veröffentlicht in: | Neoplasia (New York, N.Y.) N.Y.), 2019-01, Vol.21 (2), p.247-256 |
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| creator | Bihr, Svenja Ohashi, Riuko Moore, Ariane L. Rüschoff, Jan H. Beisel, Christian Hermanns, Thomas Mischo, Axel Corrò, Claudia Beyer, Jörg Beerenwinkel, Niko Moch, Holger Schraml, Peter |
| description | Bi-allelic inactivation of the
VHL
gene on chromosome 3p is the characteristic feature in most clear cell renal cell carcinomas (ccRCC). Frequent gene alterations were also identified in
SETD2
,
BAP1
and
PBRM1,
all of which are situated on chromosome 3p and encode histone/chromatin regulators. The relationship between gene mutation, loss of protein expression and the correlations with clinicopathological parameters is important for the understanding of renal cancer progression. We analyzed PBRM1 and BAP1 protein expression as well as the tri-methylation state of H3K36 as a surrogate marker for SETD2 activity in more than 700 RCC samples. In ccRCC loss of nuclear PBRM1 (68%), BAP1 (40%) and H3K36me3 (47%) expression was significantly correlated with each other, advanced tumor stage, poor tumor differentiation (
P
|
| doi_str_mv | 10.1016/j.neo.2018.12.006 |
| format | Article |
| fullrecord | <record><control><sourceid>pubmedcentral</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6355619</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>pubmedcentral_primary_oai_pubmedcentral_nih_gov_6355619</sourcerecordid><originalsourceid>FETCH-pubmedcentral_primary_oai_pubmedcentral_nih_gov_63556193</originalsourceid><addsrcrecordid>eNqljL9OwzAYxC0EouXPA7B9D0CC7RCnLEg0BLFEiprukZt-AVeOHdlORWdenBRYmJnuTne_I-SG0ZhRJu52sUEbc8oWMeMxpeKEzNl9JqI0XYjTyaecRwtK-YxceL-jE8Oy7JzMEioEpZmYk8_iY3DovbIGpNlCOQYZjqGSIaAzHmwH1XJVsltYPlXse1QX62cOpXLOOqgHbFWnWij2Vo9HVroD1OMmHAb0oAzkGqWDHLWGFRqpf2wuXauM7SW7Imed1B6vf_WSPL4U6_w1GsZNj9sWTXBSN4NT_XTdWKmav41R782b3TciSVPBHpJ_H3wBAfFvGA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Expression and Mutation Patterns of PBRM1, BAP1 and SETD2 Mirror Specific Evolutionary Subtypes in Clear Cell Renal Cell Carcinoma1</title><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Bihr, Svenja ; Ohashi, Riuko ; Moore, Ariane L. ; Rüschoff, Jan H. ; Beisel, Christian ; Hermanns, Thomas ; Mischo, Axel ; Corrò, Claudia ; Beyer, Jörg ; Beerenwinkel, Niko ; Moch, Holger ; Schraml, Peter</creator><creatorcontrib>Bihr, Svenja ; Ohashi, Riuko ; Moore, Ariane L. ; Rüschoff, Jan H. ; Beisel, Christian ; Hermanns, Thomas ; Mischo, Axel ; Corrò, Claudia ; Beyer, Jörg ; Beerenwinkel, Niko ; Moch, Holger ; Schraml, Peter</creatorcontrib><description>Bi-allelic inactivation of the
VHL
gene on chromosome 3p is the characteristic feature in most clear cell renal cell carcinomas (ccRCC). Frequent gene alterations were also identified in
SETD2
,
BAP1
and
PBRM1,
all of which are situated on chromosome 3p and encode histone/chromatin regulators. The relationship between gene mutation, loss of protein expression and the correlations with clinicopathological parameters is important for the understanding of renal cancer progression. We analyzed PBRM1 and BAP1 protein expression as well as the tri-methylation state of H3K36 as a surrogate marker for SETD2 activity in more than 700 RCC samples. In ccRCC loss of nuclear PBRM1 (68%), BAP1 (40%) and H3K36me3 (47%) expression was significantly correlated with each other, advanced tumor stage, poor tumor differentiation (
P
< .0001 each), and necrosis (
P
< .005) Targeted next generation sequencing of 83 ccRCC samples demonstrated a significant association of genetic mutations in
PBRM1, BAP1, and SETD2
with absence of PBRM1, BAP1, and HEK36me3 protein expression (
P
< .05, each). By assigning the protein expression patterns to evolutionary subtypes, we revealed similar clinical phenotypes as suggested by TRACERx Renal. Given their important contribution to tumor suppression, we conclude that combined functional inactivation of PBRM1, BAP1, SETD2 and pVHL is critical for ccRCC progression.</description><identifier>ISSN: 1522-8002</identifier><identifier>EISSN: 1476-5586</identifier><identifier>DOI: 10.1016/j.neo.2018.12.006</identifier><identifier>PMID: 30660076</identifier><language>eng</language><publisher>Neoplasia Press</publisher><subject>Original article</subject><ispartof>Neoplasia (New York, N.Y.), 2019-01, Vol.21 (2), p.247-256</ispartof><rights>2019 The Authors 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355619/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355619/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,862,883,27907,27908,53774,53776</link.rule.ids></links><search><creatorcontrib>Bihr, Svenja</creatorcontrib><creatorcontrib>Ohashi, Riuko</creatorcontrib><creatorcontrib>Moore, Ariane L.</creatorcontrib><creatorcontrib>Rüschoff, Jan H.</creatorcontrib><creatorcontrib>Beisel, Christian</creatorcontrib><creatorcontrib>Hermanns, Thomas</creatorcontrib><creatorcontrib>Mischo, Axel</creatorcontrib><creatorcontrib>Corrò, Claudia</creatorcontrib><creatorcontrib>Beyer, Jörg</creatorcontrib><creatorcontrib>Beerenwinkel, Niko</creatorcontrib><creatorcontrib>Moch, Holger</creatorcontrib><creatorcontrib>Schraml, Peter</creatorcontrib><title>Expression and Mutation Patterns of PBRM1, BAP1 and SETD2 Mirror Specific Evolutionary Subtypes in Clear Cell Renal Cell Carcinoma1</title><title>Neoplasia (New York, N.Y.)</title><description>Bi-allelic inactivation of the
VHL
gene on chromosome 3p is the characteristic feature in most clear cell renal cell carcinomas (ccRCC). Frequent gene alterations were also identified in
SETD2
,
BAP1
and
PBRM1,
all of which are situated on chromosome 3p and encode histone/chromatin regulators. The relationship between gene mutation, loss of protein expression and the correlations with clinicopathological parameters is important for the understanding of renal cancer progression. We analyzed PBRM1 and BAP1 protein expression as well as the tri-methylation state of H3K36 as a surrogate marker for SETD2 activity in more than 700 RCC samples. In ccRCC loss of nuclear PBRM1 (68%), BAP1 (40%) and H3K36me3 (47%) expression was significantly correlated with each other, advanced tumor stage, poor tumor differentiation (
P
< .0001 each), and necrosis (
P
< .005) Targeted next generation sequencing of 83 ccRCC samples demonstrated a significant association of genetic mutations in
PBRM1, BAP1, and SETD2
with absence of PBRM1, BAP1, and HEK36me3 protein expression (
P
< .05, each). By assigning the protein expression patterns to evolutionary subtypes, we revealed similar clinical phenotypes as suggested by TRACERx Renal. Given their important contribution to tumor suppression, we conclude that combined functional inactivation of PBRM1, BAP1, SETD2 and pVHL is critical for ccRCC progression.</description><subject>Original article</subject><issn>1522-8002</issn><issn>1476-5586</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNqljL9OwzAYxC0EouXPA7B9D0CC7RCnLEg0BLFEiprukZt-AVeOHdlORWdenBRYmJnuTne_I-SG0ZhRJu52sUEbc8oWMeMxpeKEzNl9JqI0XYjTyaecRwtK-YxceL-jE8Oy7JzMEioEpZmYk8_iY3DovbIGpNlCOQYZjqGSIaAzHmwH1XJVsltYPlXse1QX62cOpXLOOqgHbFWnWij2Vo9HVroD1OMmHAb0oAzkGqWDHLWGFRqpf2wuXauM7SW7Imed1B6vf_WSPL4U6_w1GsZNj9sWTXBSN4NT_XTdWKmav41R782b3TciSVPBHpJ_H3wBAfFvGA</recordid><startdate>20190116</startdate><enddate>20190116</enddate><creator>Bihr, Svenja</creator><creator>Ohashi, Riuko</creator><creator>Moore, Ariane L.</creator><creator>Rüschoff, Jan H.</creator><creator>Beisel, Christian</creator><creator>Hermanns, Thomas</creator><creator>Mischo, Axel</creator><creator>Corrò, Claudia</creator><creator>Beyer, Jörg</creator><creator>Beerenwinkel, Niko</creator><creator>Moch, Holger</creator><creator>Schraml, Peter</creator><general>Neoplasia Press</general><scope>5PM</scope></search><sort><creationdate>20190116</creationdate><title>Expression and Mutation Patterns of PBRM1, BAP1 and SETD2 Mirror Specific Evolutionary Subtypes in Clear Cell Renal Cell Carcinoma1</title><author>Bihr, Svenja ; Ohashi, Riuko ; Moore, Ariane L. ; Rüschoff, Jan H. ; Beisel, Christian ; Hermanns, Thomas ; Mischo, Axel ; Corrò, Claudia ; Beyer, Jörg ; Beerenwinkel, Niko ; Moch, Holger ; Schraml, Peter</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-pubmedcentral_primary_oai_pubmedcentral_nih_gov_63556193</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Original article</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bihr, Svenja</creatorcontrib><creatorcontrib>Ohashi, Riuko</creatorcontrib><creatorcontrib>Moore, Ariane L.</creatorcontrib><creatorcontrib>Rüschoff, Jan H.</creatorcontrib><creatorcontrib>Beisel, Christian</creatorcontrib><creatorcontrib>Hermanns, Thomas</creatorcontrib><creatorcontrib>Mischo, Axel</creatorcontrib><creatorcontrib>Corrò, Claudia</creatorcontrib><creatorcontrib>Beyer, Jörg</creatorcontrib><creatorcontrib>Beerenwinkel, Niko</creatorcontrib><creatorcontrib>Moch, Holger</creatorcontrib><creatorcontrib>Schraml, Peter</creatorcontrib><collection>PubMed Central (Full Participant titles)</collection><jtitle>Neoplasia (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bihr, Svenja</au><au>Ohashi, Riuko</au><au>Moore, Ariane L.</au><au>Rüschoff, Jan H.</au><au>Beisel, Christian</au><au>Hermanns, Thomas</au><au>Mischo, Axel</au><au>Corrò, Claudia</au><au>Beyer, Jörg</au><au>Beerenwinkel, Niko</au><au>Moch, Holger</au><au>Schraml, Peter</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression and Mutation Patterns of PBRM1, BAP1 and SETD2 Mirror Specific Evolutionary Subtypes in Clear Cell Renal Cell Carcinoma1</atitle><jtitle>Neoplasia (New York, N.Y.)</jtitle><date>2019-01-16</date><risdate>2019</risdate><volume>21</volume><issue>2</issue><spage>247</spage><epage>256</epage><pages>247-256</pages><issn>1522-8002</issn><eissn>1476-5586</eissn><abstract>Bi-allelic inactivation of the
VHL
gene on chromosome 3p is the characteristic feature in most clear cell renal cell carcinomas (ccRCC). Frequent gene alterations were also identified in
SETD2
,
BAP1
and
PBRM1,
all of which are situated on chromosome 3p and encode histone/chromatin regulators. The relationship between gene mutation, loss of protein expression and the correlations with clinicopathological parameters is important for the understanding of renal cancer progression. We analyzed PBRM1 and BAP1 protein expression as well as the tri-methylation state of H3K36 as a surrogate marker for SETD2 activity in more than 700 RCC samples. In ccRCC loss of nuclear PBRM1 (68%), BAP1 (40%) and H3K36me3 (47%) expression was significantly correlated with each other, advanced tumor stage, poor tumor differentiation (
P
< .0001 each), and necrosis (
P
< .005) Targeted next generation sequencing of 83 ccRCC samples demonstrated a significant association of genetic mutations in
PBRM1, BAP1, and SETD2
with absence of PBRM1, BAP1, and HEK36me3 protein expression (
P
< .05, each). By assigning the protein expression patterns to evolutionary subtypes, we revealed similar clinical phenotypes as suggested by TRACERx Renal. Given their important contribution to tumor suppression, we conclude that combined functional inactivation of PBRM1, BAP1, SETD2 and pVHL is critical for ccRCC progression.</abstract><pub>Neoplasia Press</pub><pmid>30660076</pmid><doi>10.1016/j.neo.2018.12.006</doi><oa>free_for_read</oa></addata></record> |
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| source | DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Original article |
| title | Expression and Mutation Patterns of PBRM1, BAP1 and SETD2 Mirror Specific Evolutionary Subtypes in Clear Cell Renal Cell Carcinoma1 |
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