Aberrant Epidermal Growth Factor Receptor RNA Splice Products Are Among the Most Frequent Somatic Alterations in Clear Cell Renal Cell Carcinoma and Are Associated with a Poor Response to Immunotherapy
Accumulating evidence suggests that alternative RNA splicing has an important role in cancer development and progression by driving the expression of a diverse array of RNA and protein isoforms from a handful of genes. However, our understanding of the clinical significance of cancer-specific RNA sp...
Gespeichert in:
| Veröffentlicht in: | European urology focus 2021-03, Vol.7 (2), p.373-380 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 380 |
|---|---|
| container_issue | 2 |
| container_start_page | 373 |
| container_title | European urology focus |
| container_volume | 7 |
| creator | Zaman, Saif Hajiran, Ali Coba, George A. Robinson, Timothy Madanayake, Thushara W. Segarra, Daniel T. Chobrutskiy, Boris I. Boyle, Theresa A. Zhou, Jun-Min Kim, Youngchul Mulé, James J. Teer, Jamie K. Manley, Brandon J. |
| description | Accumulating evidence suggests that alternative RNA splicing has an important role in cancer development and progression by driving the expression of a diverse array of RNA and protein isoforms from a handful of genes. However, our understanding of the clinical significance of cancer-specific RNA splicing in renal cell carcinoma (RCC) is limited.
To characterize and validate a novel oncogene RNA splicing event discovered in patients with RCC and to correlate expression with clinical outcomes.
Using DNA and RNA sequencing, we identified a novel epidermal growth factor receptor (EGFR) splicing alteration (EGFR_pr20CTF) in RCC tumor tissue.
We confirmed the frequency and specificity of the EGFR_pr20CTF variant by analyzing cohorts of patients from our institution (n = 699) and The Cancer Genome Atlas (TCGA; n = 832). Furthermore, we analyzed its expression in tumor tissue and a human kidney cancer cell line using reverse transcriptase-polymerase chain reaction. Variant expression was also correlated with survival and response to systemic therapy.
EGFR_pr20CTF expression was identified in 71.7% (n = 71/99) of patients with RCC in our institutional cohort and in 56.7% (n = 279/492) of patients in the TCGA cohort. EGFR_pr20CTF was found to be specific to clear cell renal cell carcinoma (ccRCC), occurring in |
| doi_str_mv | 10.1016/j.euf.2019.12.001 |
| format | Article |
| fullrecord | <record><control><sourceid>elsevier_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7771328</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S2405456919303797</els_id><sourcerecordid>S2405456919303797</sourcerecordid><originalsourceid>FETCH-LOGICAL-c451t-1762c4a54b0e587b7f346187ffc8489788bc3f1c4713a6aa2c007b4b2c6e8da03</originalsourceid><addsrcrecordid>eNp9kdFq3DAQRU1paUKSD-hLmR9YV7JlS0uhYEw2DaRNaNpnIcvjrBZbciU5IZ_Yv6qy24b0pU-6oHvPzHCz7B0lOSW0_rDLcRnygtB1ToucEPoqOy4YqVasqtevX-ij7CyEHUmOivFSlG-zo5KuCWWlOM5-NR16r2yE89n06Cc1woV3D3ELG6Wj8_ANNc578bWB23k0GuHGu37RMUDjEZrJ2TuIW4QvLkTYePy5YALeuklFo6EZI_qknA1gLLQjKg8tjmNC2zRuL1vltbEpAcr2B2wIThsVsYcHk9ZRcOP264Q5kRCig8tpWqxLk72aH0-zN4MaA579eU-yH5vz7-3n1dX1xWXbXK00q2hcUV4XmqmKdQQrwTs-lKymgg-DFkysuRCdLgeqGaelqpUqNCG8Y12haxS9IuVJ9unAnZduwl6nU70a5ezNpPyjdMrIf3-s2co7dy85T8hCJAA9ALR3IXgcnrOUyKdq5U6mauVTtZIWMhWXMu9fDn1O_C0yGT4eDJhOvzfoZdAGrcbeeNRR9s78B_8bY724cA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Aberrant Epidermal Growth Factor Receptor RNA Splice Products Are Among the Most Frequent Somatic Alterations in Clear Cell Renal Cell Carcinoma and Are Associated with a Poor Response to Immunotherapy</title><source>MEDLINE</source><source>Alma/SFX Local Collection</source><creator>Zaman, Saif ; Hajiran, Ali ; Coba, George A. ; Robinson, Timothy ; Madanayake, Thushara W. ; Segarra, Daniel T. ; Chobrutskiy, Boris I. ; Boyle, Theresa A. ; Zhou, Jun-Min ; Kim, Youngchul ; Mulé, James J. ; Teer, Jamie K. ; Manley, Brandon J.</creator><creatorcontrib>Zaman, Saif ; Hajiran, Ali ; Coba, George A. ; Robinson, Timothy ; Madanayake, Thushara W. ; Segarra, Daniel T. ; Chobrutskiy, Boris I. ; Boyle, Theresa A. ; Zhou, Jun-Min ; Kim, Youngchul ; Mulé, James J. ; Teer, Jamie K. ; Manley, Brandon J.</creatorcontrib><description>Accumulating evidence suggests that alternative RNA splicing has an important role in cancer development and progression by driving the expression of a diverse array of RNA and protein isoforms from a handful of genes. However, our understanding of the clinical significance of cancer-specific RNA splicing in renal cell carcinoma (RCC) is limited.
To characterize and validate a novel oncogene RNA splicing event discovered in patients with RCC and to correlate expression with clinical outcomes.
Using DNA and RNA sequencing, we identified a novel epidermal growth factor receptor (EGFR) splicing alteration (EGFR_pr20CTF) in RCC tumor tissue.
We confirmed the frequency and specificity of the EGFR_pr20CTF variant by analyzing cohorts of patients from our institution (n = 699) and The Cancer Genome Atlas (TCGA; n = 832). Furthermore, we analyzed its expression in tumor tissue and a human kidney cancer cell line using reverse transcriptase-polymerase chain reaction. Variant expression was also correlated with survival and response to systemic therapy.
EGFR_pr20CTF expression was identified in 71.7% (n = 71/99) of patients with RCC in our institutional cohort and in 56.7% (n = 279/492) of patients in the TCGA cohort. EGFR_pr20CTF was found to be specific to clear cell renal cell carcinoma (ccRCC), occurring in <0.2% of non-RCC tumors (n = 2/1091). High levels of EGFR_pr20CTF correlated with lower survival at 48 mo following immunotherapy (p = 0.036). The average survival in patients with high EGFR_pr20CTF expression was <16 mo.
The EGFR_pr20CTF RNA splice variant occurs frequently, is specific to patients with advanced ccRCC, and is associated with a poor response to immunotherapy.
Cancer-specific RNA alternative splicing may portend a poor prognosis in patients with advanced clear cell renal cell carcinoma. Further investigation will help clarify whether EGFR_pr20CTF can be used as a biomarker for this patient population.
In this study, we characterize a novel oncogene RNA splicing event discovered in patients with renal cell carcinoma (RCC). This event occurs frequently, is specific to patients with advanced RCC, and is associated with a poor response to immunotherapy.</description><identifier>ISSN: 2405-4569</identifier><identifier>EISSN: 2405-4569</identifier><identifier>DOI: 10.1016/j.euf.2019.12.001</identifier><identifier>PMID: 31901438</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Carcinoma, Renal Cell - genetics ; Carcinoma, Renal Cell - metabolism ; Carcinoma, Renal Cell - therapy ; Epidermal growth factor receptor ; ErbB Receptors - genetics ; Gene Expression ; Humans ; Immunotherapy ; Kidney Neoplasms - genetics ; Kidney Neoplasms - metabolism ; Kidney Neoplasms - therapy ; Prognosis ; Renal cell carcinoma ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; RNA ; RNA sequencing ; RNA splice variants</subject><ispartof>European urology focus, 2021-03, Vol.7 (2), p.373-380</ispartof><rights>2019 European Association of Urology</rights><rights>Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c451t-1762c4a54b0e587b7f346187ffc8489788bc3f1c4713a6aa2c007b4b2c6e8da03</citedby><cites>FETCH-LOGICAL-c451t-1762c4a54b0e587b7f346187ffc8489788bc3f1c4713a6aa2c007b4b2c6e8da03</cites><orcidid>0000-0002-1465-9821 ; 0000-0003-4513-0282 ; 0000-0001-5950-3970 ; 0000-0002-2307-0330</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31901438$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zaman, Saif</creatorcontrib><creatorcontrib>Hajiran, Ali</creatorcontrib><creatorcontrib>Coba, George A.</creatorcontrib><creatorcontrib>Robinson, Timothy</creatorcontrib><creatorcontrib>Madanayake, Thushara W.</creatorcontrib><creatorcontrib>Segarra, Daniel T.</creatorcontrib><creatorcontrib>Chobrutskiy, Boris I.</creatorcontrib><creatorcontrib>Boyle, Theresa A.</creatorcontrib><creatorcontrib>Zhou, Jun-Min</creatorcontrib><creatorcontrib>Kim, Youngchul</creatorcontrib><creatorcontrib>Mulé, James J.</creatorcontrib><creatorcontrib>Teer, Jamie K.</creatorcontrib><creatorcontrib>Manley, Brandon J.</creatorcontrib><title>Aberrant Epidermal Growth Factor Receptor RNA Splice Products Are Among the Most Frequent Somatic Alterations in Clear Cell Renal Cell Carcinoma and Are Associated with a Poor Response to Immunotherapy</title><title>European urology focus</title><addtitle>Eur Urol Focus</addtitle><description>Accumulating evidence suggests that alternative RNA splicing has an important role in cancer development and progression by driving the expression of a diverse array of RNA and protein isoforms from a handful of genes. However, our understanding of the clinical significance of cancer-specific RNA splicing in renal cell carcinoma (RCC) is limited.
To characterize and validate a novel oncogene RNA splicing event discovered in patients with RCC and to correlate expression with clinical outcomes.
Using DNA and RNA sequencing, we identified a novel epidermal growth factor receptor (EGFR) splicing alteration (EGFR_pr20CTF) in RCC tumor tissue.
We confirmed the frequency and specificity of the EGFR_pr20CTF variant by analyzing cohorts of patients from our institution (n = 699) and The Cancer Genome Atlas (TCGA; n = 832). Furthermore, we analyzed its expression in tumor tissue and a human kidney cancer cell line using reverse transcriptase-polymerase chain reaction. Variant expression was also correlated with survival and response to systemic therapy.
EGFR_pr20CTF expression was identified in 71.7% (n = 71/99) of patients with RCC in our institutional cohort and in 56.7% (n = 279/492) of patients in the TCGA cohort. EGFR_pr20CTF was found to be specific to clear cell renal cell carcinoma (ccRCC), occurring in <0.2% of non-RCC tumors (n = 2/1091). High levels of EGFR_pr20CTF correlated with lower survival at 48 mo following immunotherapy (p = 0.036). The average survival in patients with high EGFR_pr20CTF expression was <16 mo.
The EGFR_pr20CTF RNA splice variant occurs frequently, is specific to patients with advanced ccRCC, and is associated with a poor response to immunotherapy.
Cancer-specific RNA alternative splicing may portend a poor prognosis in patients with advanced clear cell renal cell carcinoma. Further investigation will help clarify whether EGFR_pr20CTF can be used as a biomarker for this patient population.
In this study, we characterize a novel oncogene RNA splicing event discovered in patients with renal cell carcinoma (RCC). This event occurs frequently, is specific to patients with advanced RCC, and is associated with a poor response to immunotherapy.</description><subject>Carcinoma, Renal Cell - genetics</subject><subject>Carcinoma, Renal Cell - metabolism</subject><subject>Carcinoma, Renal Cell - therapy</subject><subject>Epidermal growth factor receptor</subject><subject>ErbB Receptors - genetics</subject><subject>Gene Expression</subject><subject>Humans</subject><subject>Immunotherapy</subject><subject>Kidney Neoplasms - genetics</subject><subject>Kidney Neoplasms - metabolism</subject><subject>Kidney Neoplasms - therapy</subject><subject>Prognosis</subject><subject>Renal cell carcinoma</subject><subject>Retrospective Studies</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA</subject><subject>RNA sequencing</subject><subject>RNA splice variants</subject><issn>2405-4569</issn><issn>2405-4569</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kdFq3DAQRU1paUKSD-hLmR9YV7JlS0uhYEw2DaRNaNpnIcvjrBZbciU5IZ_Yv6qy24b0pU-6oHvPzHCz7B0lOSW0_rDLcRnygtB1ToucEPoqOy4YqVasqtevX-ij7CyEHUmOivFSlG-zo5KuCWWlOM5-NR16r2yE89n06Cc1woV3D3ELG6Wj8_ANNc578bWB23k0GuHGu37RMUDjEZrJ2TuIW4QvLkTYePy5YALeuklFo6EZI_qknA1gLLQjKg8tjmNC2zRuL1vltbEpAcr2B2wIThsVsYcHk9ZRcOP264Q5kRCig8tpWqxLk72aH0-zN4MaA579eU-yH5vz7-3n1dX1xWXbXK00q2hcUV4XmqmKdQQrwTs-lKymgg-DFkysuRCdLgeqGaelqpUqNCG8Y12haxS9IuVJ9unAnZduwl6nU70a5ezNpPyjdMrIf3-s2co7dy85T8hCJAA9ALR3IXgcnrOUyKdq5U6mauVTtZIWMhWXMu9fDn1O_C0yGT4eDJhOvzfoZdAGrcbeeNRR9s78B_8bY724cA</recordid><startdate>20210301</startdate><enddate>20210301</enddate><creator>Zaman, Saif</creator><creator>Hajiran, Ali</creator><creator>Coba, George A.</creator><creator>Robinson, Timothy</creator><creator>Madanayake, Thushara W.</creator><creator>Segarra, Daniel T.</creator><creator>Chobrutskiy, Boris I.</creator><creator>Boyle, Theresa A.</creator><creator>Zhou, Jun-Min</creator><creator>Kim, Youngchul</creator><creator>Mulé, James J.</creator><creator>Teer, Jamie K.</creator><creator>Manley, Brandon J.</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1465-9821</orcidid><orcidid>https://orcid.org/0000-0003-4513-0282</orcidid><orcidid>https://orcid.org/0000-0001-5950-3970</orcidid><orcidid>https://orcid.org/0000-0002-2307-0330</orcidid></search><sort><creationdate>20210301</creationdate><title>Aberrant Epidermal Growth Factor Receptor RNA Splice Products Are Among the Most Frequent Somatic Alterations in Clear Cell Renal Cell Carcinoma and Are Associated with a Poor Response to Immunotherapy</title><author>Zaman, Saif ; Hajiran, Ali ; Coba, George A. ; Robinson, Timothy ; Madanayake, Thushara W. ; Segarra, Daniel T. ; Chobrutskiy, Boris I. ; Boyle, Theresa A. ; Zhou, Jun-Min ; Kim, Youngchul ; Mulé, James J. ; Teer, Jamie K. ; Manley, Brandon J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c451t-1762c4a54b0e587b7f346187ffc8489788bc3f1c4713a6aa2c007b4b2c6e8da03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Carcinoma, Renal Cell - genetics</topic><topic>Carcinoma, Renal Cell - metabolism</topic><topic>Carcinoma, Renal Cell - therapy</topic><topic>Epidermal growth factor receptor</topic><topic>ErbB Receptors - genetics</topic><topic>Gene Expression</topic><topic>Humans</topic><topic>Immunotherapy</topic><topic>Kidney Neoplasms - genetics</topic><topic>Kidney Neoplasms - metabolism</topic><topic>Kidney Neoplasms - therapy</topic><topic>Prognosis</topic><topic>Renal cell carcinoma</topic><topic>Retrospective Studies</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA</topic><topic>RNA sequencing</topic><topic>RNA splice variants</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zaman, Saif</creatorcontrib><creatorcontrib>Hajiran, Ali</creatorcontrib><creatorcontrib>Coba, George A.</creatorcontrib><creatorcontrib>Robinson, Timothy</creatorcontrib><creatorcontrib>Madanayake, Thushara W.</creatorcontrib><creatorcontrib>Segarra, Daniel T.</creatorcontrib><creatorcontrib>Chobrutskiy, Boris I.</creatorcontrib><creatorcontrib>Boyle, Theresa A.</creatorcontrib><creatorcontrib>Zhou, Jun-Min</creatorcontrib><creatorcontrib>Kim, Youngchul</creatorcontrib><creatorcontrib>Mulé, James J.</creatorcontrib><creatorcontrib>Teer, Jamie K.</creatorcontrib><creatorcontrib>Manley, Brandon J.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>European urology focus</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zaman, Saif</au><au>Hajiran, Ali</au><au>Coba, George A.</au><au>Robinson, Timothy</au><au>Madanayake, Thushara W.</au><au>Segarra, Daniel T.</au><au>Chobrutskiy, Boris I.</au><au>Boyle, Theresa A.</au><au>Zhou, Jun-Min</au><au>Kim, Youngchul</au><au>Mulé, James J.</au><au>Teer, Jamie K.</au><au>Manley, Brandon J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Aberrant Epidermal Growth Factor Receptor RNA Splice Products Are Among the Most Frequent Somatic Alterations in Clear Cell Renal Cell Carcinoma and Are Associated with a Poor Response to Immunotherapy</atitle><jtitle>European urology focus</jtitle><addtitle>Eur Urol Focus</addtitle><date>2021-03-01</date><risdate>2021</risdate><volume>7</volume><issue>2</issue><spage>373</spage><epage>380</epage><pages>373-380</pages><issn>2405-4569</issn><eissn>2405-4569</eissn><abstract>Accumulating evidence suggests that alternative RNA splicing has an important role in cancer development and progression by driving the expression of a diverse array of RNA and protein isoforms from a handful of genes. However, our understanding of the clinical significance of cancer-specific RNA splicing in renal cell carcinoma (RCC) is limited.
To characterize and validate a novel oncogene RNA splicing event discovered in patients with RCC and to correlate expression with clinical outcomes.
Using DNA and RNA sequencing, we identified a novel epidermal growth factor receptor (EGFR) splicing alteration (EGFR_pr20CTF) in RCC tumor tissue.
We confirmed the frequency and specificity of the EGFR_pr20CTF variant by analyzing cohorts of patients from our institution (n = 699) and The Cancer Genome Atlas (TCGA; n = 832). Furthermore, we analyzed its expression in tumor tissue and a human kidney cancer cell line using reverse transcriptase-polymerase chain reaction. Variant expression was also correlated with survival and response to systemic therapy.
EGFR_pr20CTF expression was identified in 71.7% (n = 71/99) of patients with RCC in our institutional cohort and in 56.7% (n = 279/492) of patients in the TCGA cohort. EGFR_pr20CTF was found to be specific to clear cell renal cell carcinoma (ccRCC), occurring in <0.2% of non-RCC tumors (n = 2/1091). High levels of EGFR_pr20CTF correlated with lower survival at 48 mo following immunotherapy (p = 0.036). The average survival in patients with high EGFR_pr20CTF expression was <16 mo.
The EGFR_pr20CTF RNA splice variant occurs frequently, is specific to patients with advanced ccRCC, and is associated with a poor response to immunotherapy.
Cancer-specific RNA alternative splicing may portend a poor prognosis in patients with advanced clear cell renal cell carcinoma. Further investigation will help clarify whether EGFR_pr20CTF can be used as a biomarker for this patient population.
In this study, we characterize a novel oncogene RNA splicing event discovered in patients with renal cell carcinoma (RCC). This event occurs frequently, is specific to patients with advanced RCC, and is associated with a poor response to immunotherapy.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>31901438</pmid><doi>10.1016/j.euf.2019.12.001</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-1465-9821</orcidid><orcidid>https://orcid.org/0000-0003-4513-0282</orcidid><orcidid>https://orcid.org/0000-0001-5950-3970</orcidid><orcidid>https://orcid.org/0000-0002-2307-0330</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2405-4569 |
| ispartof | European urology focus, 2021-03, Vol.7 (2), p.373-380 |
| issn | 2405-4569 2405-4569 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7771328 |
| source | MEDLINE; Alma/SFX Local Collection |
| subjects | Carcinoma, Renal Cell - genetics Carcinoma, Renal Cell - metabolism Carcinoma, Renal Cell - therapy Epidermal growth factor receptor ErbB Receptors - genetics Gene Expression Humans Immunotherapy Kidney Neoplasms - genetics Kidney Neoplasms - metabolism Kidney Neoplasms - therapy Prognosis Renal cell carcinoma Retrospective Studies Reverse Transcriptase Polymerase Chain Reaction RNA RNA sequencing RNA splice variants |
| title | Aberrant Epidermal Growth Factor Receptor RNA Splice Products Are Among the Most Frequent Somatic Alterations in Clear Cell Renal Cell Carcinoma and Are Associated with a Poor Response to Immunotherapy |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-09T02%3A58%3A33IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-elsevier_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Aberrant%20Epidermal%20Growth%20Factor%20Receptor%20RNA%20Splice%20Products%20Are%20Among%20the%20Most%20Frequent%20Somatic%20Alterations%20in%20Clear%20Cell%20Renal%20Cell%20Carcinoma%20and%20Are%20Associated%20with%20a%20Poor%20Response%20to%20Immunotherapy&rft.jtitle=European%20urology%20focus&rft.au=Zaman,%20Saif&rft.date=2021-03-01&rft.volume=7&rft.issue=2&rft.spage=373&rft.epage=380&rft.pages=373-380&rft.issn=2405-4569&rft.eissn=2405-4569&rft_id=info:doi/10.1016/j.euf.2019.12.001&rft_dat=%3Celsevier_pubme%3ES2405456919303797%3C/elsevier_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/31901438&rft_els_id=S2405456919303797&rfr_iscdi=true |