KMT2D Mutation Is Associated With Poor Prognosis in Non–Small-Cell Lung Cancer
The present retrospective study evaluated the association of mutations in KMT2D, an epigenetic regulator, with survival in non–small-cell lung cancer (NSCLC) and compared it with small-cell lung cancer (SCLC). Tumors from 194 patients with locally advanced or advanced NSCLC and 64 patients with SCLC...
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| Veröffentlicht in: | Clinical lung cancer 2018-07, Vol.19 (4), p.e489-e501 |
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| creator | Ardeshir-Larijani, Fatemeh Bhateja, Priyanka Lipka, Mary Beth Sharma, Neelesh Fu, Pingfu Dowlati, Afshin |
| description | The present retrospective study evaluated the association of mutations in KMT2D, an epigenetic regulator, with survival in non–small-cell lung cancer (NSCLC) and compared it with small-cell lung cancer (SCLC). Tumors from 194 patients with locally advanced or advanced NSCLC and 64 patients with SCLC underwent targeted-exome sequencing. The KMT2D mutation rate was 17.5% in NSCLC and 32.8% in SCLC. KMT2D mutation is associated with reduced survival in NSCLC but not SCLC.
Mixed-lineage leukemia protein 2 (MLL2 or KMT2D) is a histone methyltransferase whose mutation has been associated with a poor prognosis in cancer. We compared the characteristics and significance of KMT2D alterations in non–small-cell lung cancer (NSCLC) with those in small cell lung cancer (SCLC).
Tumors from 194 NSCLC patients with locally advanced or advanced disease and 64 SCLC patients underwent targeted-exome sequencing. The association of KMT2D mutation with overall survival (OS) and progression-free survival (PFS) was measured using Kaplan-Meier methods and further evaluated using multivariable Cox proportional hazards regression model adjusting for known clinical prognostic features.
The KMT2D mutation rate was 17.5% (34 of 194) in NSCLC. Patients with mutant KMT2D had significantly lower median OS (9.97 vs. 30.2 months; P < .0001) and median PFS (8.46 vs. 24.1 months; P = .0004) compared with patients with wild-type KMT2D. The KMT2D mutation was significantly more common in females (P = .017). Using a multivariate Cox regression model, KMT2D mutation was one of the most significant prognostic factors in NSCLC: hazard ratio (HR) for OS, 2.79 (95% confidence interval [CI], 1.8-4.33; P < .0001) and HR for PFS, 1.99 (95% CI, 1.32-3.01; P = .001). In contrast, the KMT2D mutation rate in SCLC was 32.8% (21 of 64) and showed no sex bias (P = .874). No significant change was found in survival in association with the KMT2D mutation in SCLC (OS, P = .952; PFS, P = .744).
The KMT2D mutation was associated with reduced survival in NSCLC but not in SCLC. |
| doi_str_mv | 10.1016/j.cllc.2018.03.005 |
| format | Article |
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Mixed-lineage leukemia protein 2 (MLL2 or KMT2D) is a histone methyltransferase whose mutation has been associated with a poor prognosis in cancer. We compared the characteristics and significance of KMT2D alterations in non–small-cell lung cancer (NSCLC) with those in small cell lung cancer (SCLC).
Tumors from 194 NSCLC patients with locally advanced or advanced disease and 64 SCLC patients underwent targeted-exome sequencing. The association of KMT2D mutation with overall survival (OS) and progression-free survival (PFS) was measured using Kaplan-Meier methods and further evaluated using multivariable Cox proportional hazards regression model adjusting for known clinical prognostic features.
The KMT2D mutation rate was 17.5% (34 of 194) in NSCLC. Patients with mutant KMT2D had significantly lower median OS (9.97 vs. 30.2 months; P < .0001) and median PFS (8.46 vs. 24.1 months; P = .0004) compared with patients with wild-type KMT2D. The KMT2D mutation was significantly more common in females (P = .017). Using a multivariate Cox regression model, KMT2D mutation was one of the most significant prognostic factors in NSCLC: hazard ratio (HR) for OS, 2.79 (95% confidence interval [CI], 1.8-4.33; P < .0001) and HR for PFS, 1.99 (95% CI, 1.32-3.01; P = .001). In contrast, the KMT2D mutation rate in SCLC was 32.8% (21 of 64) and showed no sex bias (P = .874). No significant change was found in survival in association with the KMT2D mutation in SCLC (OS, P = .952; PFS, P = .744).
The KMT2D mutation was associated with reduced survival in NSCLC but not in SCLC.</description><identifier>ISSN: 1525-7304</identifier><identifier>EISSN: 1938-0690</identifier><identifier>DOI: 10.1016/j.cllc.2018.03.005</identifier><identifier>PMID: 29627316</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; Aged ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - mortality ; Cohort Studies ; Disease-Free Survival ; DNA-Binding Proteins - genetics ; Epigenetics ; Exome sequencing ; Female ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms - genetics ; Lung Neoplasms - mortality ; Male ; Middle Aged ; Mixed-lineage leukemia protein 2 ; MLL2 ; Mutation ; Neoplasm Proteins - genetics ; Prognosis ; Proportional Hazards Models ; Small Cell Lung Carcinoma - genetics ; Small Cell Lung Carcinoma - mortality ; Survival analysis ; Treatment Outcome</subject><ispartof>Clinical lung cancer, 2018-07, Vol.19 (4), p.e489-e501</ispartof><rights>2018 Elsevier Inc.</rights><rights>Copyright © 2018 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-e5063e683dc85dedf9f2b709476938b79c50b7052f6b51862bbc4bf71c188b273</citedby><cites>FETCH-LOGICAL-c356t-e5063e683dc85dedf9f2b709476938b79c50b7052f6b51862bbc4bf71c188b273</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.cllc.2018.03.005$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29627316$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ardeshir-Larijani, Fatemeh</creatorcontrib><creatorcontrib>Bhateja, Priyanka</creatorcontrib><creatorcontrib>Lipka, Mary Beth</creatorcontrib><creatorcontrib>Sharma, Neelesh</creatorcontrib><creatorcontrib>Fu, Pingfu</creatorcontrib><creatorcontrib>Dowlati, Afshin</creatorcontrib><title>KMT2D Mutation Is Associated With Poor Prognosis in Non–Small-Cell Lung Cancer</title><title>Clinical lung cancer</title><addtitle>Clin Lung Cancer</addtitle><description>The present retrospective study evaluated the association of mutations in KMT2D, an epigenetic regulator, with survival in non–small-cell lung cancer (NSCLC) and compared it with small-cell lung cancer (SCLC). Tumors from 194 patients with locally advanced or advanced NSCLC and 64 patients with SCLC underwent targeted-exome sequencing. The KMT2D mutation rate was 17.5% in NSCLC and 32.8% in SCLC. KMT2D mutation is associated with reduced survival in NSCLC but not SCLC.
Mixed-lineage leukemia protein 2 (MLL2 or KMT2D) is a histone methyltransferase whose mutation has been associated with a poor prognosis in cancer. We compared the characteristics and significance of KMT2D alterations in non–small-cell lung cancer (NSCLC) with those in small cell lung cancer (SCLC).
Tumors from 194 NSCLC patients with locally advanced or advanced disease and 64 SCLC patients underwent targeted-exome sequencing. The association of KMT2D mutation with overall survival (OS) and progression-free survival (PFS) was measured using Kaplan-Meier methods and further evaluated using multivariable Cox proportional hazards regression model adjusting for known clinical prognostic features.
The KMT2D mutation rate was 17.5% (34 of 194) in NSCLC. Patients with mutant KMT2D had significantly lower median OS (9.97 vs. 30.2 months; P < .0001) and median PFS (8.46 vs. 24.1 months; P = .0004) compared with patients with wild-type KMT2D. The KMT2D mutation was significantly more common in females (P = .017). Using a multivariate Cox regression model, KMT2D mutation was one of the most significant prognostic factors in NSCLC: hazard ratio (HR) for OS, 2.79 (95% confidence interval [CI], 1.8-4.33; P < .0001) and HR for PFS, 1.99 (95% CI, 1.32-3.01; P = .001). In contrast, the KMT2D mutation rate in SCLC was 32.8% (21 of 64) and showed no sex bias (P = .874). No significant change was found in survival in association with the KMT2D mutation in SCLC (OS, P = .952; PFS, P = .744).
The KMT2D mutation was associated with reduced survival in NSCLC but not in SCLC.</description><subject>Adult</subject><subject>Aged</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - mortality</subject><subject>Cohort Studies</subject><subject>Disease-Free Survival</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Epigenetics</subject><subject>Exome sequencing</subject><subject>Female</subject><subject>Humans</subject><subject>Kaplan-Meier Estimate</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - mortality</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mixed-lineage leukemia protein 2</subject><subject>MLL2</subject><subject>Mutation</subject><subject>Neoplasm Proteins - genetics</subject><subject>Prognosis</subject><subject>Proportional Hazards Models</subject><subject>Small Cell Lung Carcinoma - genetics</subject><subject>Small Cell Lung Carcinoma - mortality</subject><subject>Survival analysis</subject><subject>Treatment Outcome</subject><issn>1525-7304</issn><issn>1938-0690</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1OwzAQhS0EgvJzARbISzYJY7t2HIlNVX5FC5UAsbQSxwFXaVzsBIkdd-CGnARXBZasZkZ672neh9AhgZQAESfzVDeNTikQmQJLAfgGGpCcyQREDptx55QnGYPhDtoNYQ5ABSN0G-3QXNCMETFAs5vpAz3D074rOutafB3wKASnbdGZCj_Z7gXPnPN45t1z64IN2Lb41rVfH5_3i6JpkrFpGjzp22c8Llpt_D7aqosmmIOfuYceL84fxlfJ5O7yejyaJJpx0SWGg2BGSFZpyStT1XlNywzyYSZigTLLNYd4c1qLkhMpaFnqYVlnRBMpy_j8Hjpe5y69e-1N6NTCBh2fKVrj-qAoUDYESeRKStdS7V0I3tRq6e2i8O-KgFqRVHO1IqlWJBUwFUlG09FPfl8uTPVn-UUXBadrgYkt36zxKmhrIoLKeqM7VTn7X_43BMyDcQ</recordid><startdate>201807</startdate><enddate>201807</enddate><creator>Ardeshir-Larijani, Fatemeh</creator><creator>Bhateja, Priyanka</creator><creator>Lipka, Mary Beth</creator><creator>Sharma, Neelesh</creator><creator>Fu, Pingfu</creator><creator>Dowlati, Afshin</creator><general>Elsevier Inc</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>7X8</scope></search><sort><creationdate>201807</creationdate><title>KMT2D Mutation Is Associated With Poor Prognosis in Non–Small-Cell Lung Cancer</title><author>Ardeshir-Larijani, Fatemeh ; Bhateja, Priyanka ; Lipka, Mary Beth ; Sharma, Neelesh ; Fu, Pingfu ; Dowlati, Afshin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-e5063e683dc85dedf9f2b709476938b79c50b7052f6b51862bbc4bf71c188b273</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Carcinoma, Non-Small-Cell Lung - mortality</topic><topic>Cohort Studies</topic><topic>Disease-Free Survival</topic><topic>DNA-Binding Proteins - genetics</topic><topic>Epigenetics</topic><topic>Exome sequencing</topic><topic>Female</topic><topic>Humans</topic><topic>Kaplan-Meier Estimate</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - mortality</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mixed-lineage leukemia protein 2</topic><topic>MLL2</topic><topic>Mutation</topic><topic>Neoplasm Proteins - genetics</topic><topic>Prognosis</topic><topic>Proportional Hazards Models</topic><topic>Small Cell Lung Carcinoma - genetics</topic><topic>Small Cell Lung Carcinoma - mortality</topic><topic>Survival analysis</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ardeshir-Larijani, Fatemeh</creatorcontrib><creatorcontrib>Bhateja, Priyanka</creatorcontrib><creatorcontrib>Lipka, Mary Beth</creatorcontrib><creatorcontrib>Sharma, Neelesh</creatorcontrib><creatorcontrib>Fu, Pingfu</creatorcontrib><creatorcontrib>Dowlati, Afshin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical lung cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ardeshir-Larijani, Fatemeh</au><au>Bhateja, Priyanka</au><au>Lipka, Mary Beth</au><au>Sharma, Neelesh</au><au>Fu, Pingfu</au><au>Dowlati, Afshin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>KMT2D Mutation Is Associated With Poor Prognosis in Non–Small-Cell Lung Cancer</atitle><jtitle>Clinical lung cancer</jtitle><addtitle>Clin Lung Cancer</addtitle><date>2018-07</date><risdate>2018</risdate><volume>19</volume><issue>4</issue><spage>e489</spage><epage>e501</epage><pages>e489-e501</pages><issn>1525-7304</issn><eissn>1938-0690</eissn><abstract>The present retrospective study evaluated the association of mutations in KMT2D, an epigenetic regulator, with survival in non–small-cell lung cancer (NSCLC) and compared it with small-cell lung cancer (SCLC). Tumors from 194 patients with locally advanced or advanced NSCLC and 64 patients with SCLC underwent targeted-exome sequencing. The KMT2D mutation rate was 17.5% in NSCLC and 32.8% in SCLC. KMT2D mutation is associated with reduced survival in NSCLC but not SCLC.
Mixed-lineage leukemia protein 2 (MLL2 or KMT2D) is a histone methyltransferase whose mutation has been associated with a poor prognosis in cancer. We compared the characteristics and significance of KMT2D alterations in non–small-cell lung cancer (NSCLC) with those in small cell lung cancer (SCLC).
Tumors from 194 NSCLC patients with locally advanced or advanced disease and 64 SCLC patients underwent targeted-exome sequencing. The association of KMT2D mutation with overall survival (OS) and progression-free survival (PFS) was measured using Kaplan-Meier methods and further evaluated using multivariable Cox proportional hazards regression model adjusting for known clinical prognostic features.
The KMT2D mutation rate was 17.5% (34 of 194) in NSCLC. Patients with mutant KMT2D had significantly lower median OS (9.97 vs. 30.2 months; P < .0001) and median PFS (8.46 vs. 24.1 months; P = .0004) compared with patients with wild-type KMT2D. The KMT2D mutation was significantly more common in females (P = .017). Using a multivariate Cox regression model, KMT2D mutation was one of the most significant prognostic factors in NSCLC: hazard ratio (HR) for OS, 2.79 (95% confidence interval [CI], 1.8-4.33; P < .0001) and HR for PFS, 1.99 (95% CI, 1.32-3.01; P = .001). In contrast, the KMT2D mutation rate in SCLC was 32.8% (21 of 64) and showed no sex bias (P = .874). No significant change was found in survival in association with the KMT2D mutation in SCLC (OS, P = .952; PFS, P = .744).
The KMT2D mutation was associated with reduced survival in NSCLC but not in SCLC.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>29627316</pmid><doi>10.1016/j.cllc.2018.03.005</doi></addata></record> |
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| subjects | Adult Aged Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - mortality Cohort Studies Disease-Free Survival DNA-Binding Proteins - genetics Epigenetics Exome sequencing Female Humans Kaplan-Meier Estimate Lung Neoplasms - genetics Lung Neoplasms - mortality Male Middle Aged Mixed-lineage leukemia protein 2 MLL2 Mutation Neoplasm Proteins - genetics Prognosis Proportional Hazards Models Small Cell Lung Carcinoma - genetics Small Cell Lung Carcinoma - mortality Survival analysis Treatment Outcome |
| title | KMT2D Mutation Is Associated With Poor Prognosis in Non–Small-Cell Lung Cancer |
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