Genetic landscape of extreme responders with anaplastic oligodendroglioma
The NRG Oncology RTOG 9402 trial showed significant survival benefit in patients with 1p/19q co-deleted anaplastic oligodendrogliomas (AO) who received both radiation (RT) and chemotherapy (PCV regimen) versus RT alone. Substantial separation of the survival curves was only seen after 7.3 years. We...
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| creator | Holdhoff, Matthias Cairncross, Gregory J Kollmeyer, Thomas M Zhang, Ming Zhang, Peixin Mehta, Minesh P Werner-Wasik, Maria Souhami, Luis Bahary, Jean-Paul Kwok, Young Hartford, Alan C Chakravarti, Arnab Yegnasubramanian, Srinivasan Vogelstein, Bert Papadopoulos, Nickolas Kinzler, Kenneth Jenkins, Robert B Bettegowda, Chetan |
| description | The NRG Oncology RTOG 9402 trial showed significant survival benefit in patients with 1p/19q co-deleted anaplastic oligodendrogliomas (AO) who received both radiation (RT) and chemotherapy (PCV regimen) versus RT alone. Substantial separation of the survival curves was only seen after 7.3 years. We aimed to determine whether there are specific genetic alterations that distinguish co-deleted AO patients who benefit from the addition of PCV from those who do not.
We performed whole exome sequencing on matched tumor and normal DNA from all available short-term (STS) and long-term survivors (LTS) who received RT+PCV. hTERT status and rs55705857 genotypes (G-allele) were analyzed in both cohorts.
Six STS (survival of |
| doi_str_mv | 10.18632/oncotarget.16773 |
| format | Article |
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We performed whole exome sequencing on matched tumor and normal DNA from all available short-term (STS) and long-term survivors (LTS) who received RT+PCV. hTERT status and rs55705857 genotypes (G-allele) were analyzed in both cohorts.
Six STS (survival of <7.3y) and 7 LTS (survival of ≥7.3y and no progression) had sufficient material for analysis. There was no significant difference between the groups regarding age, performance status and extent of resection. On average, STS had 7 and LTS 4 mutations. Most common mutations in STS vs. LTS were: IDH1 (67 vs. 86%), CIC (50 vs. 71%) and FUBP1 (17 vs. 71%). The hTERT promoter was mutated in 83% STS and 86% LTS. Genotyping of rs55705857 showed a higher prevalence of G allele carriers in LTS than STS (43 vs. 17%).
These findings confirm that IDH, CIC, FUBP1 mutations and rs55705857 genotype are common in AO. No distinct genetic signature was identified to differentiate STS and LTS.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.16773</identifier><identifier>PMID: 28388591</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>Adult ; Aged ; Alleles ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Biomarkers, Tumor ; Brain Neoplasms - drug therapy ; Brain Neoplasms - genetics ; Brain Neoplasms - mortality ; Brain Neoplasms - pathology ; Chromosome Aberrations ; Chromosomes, Human, Pair 1 ; Chromosomes, Human, Pair 19 ; Female ; Genetic Variation ; Humans ; Male ; Middle Aged ; Mutation ; Neoplasm Grading ; Oligodendroglioma - drug therapy ; Oligodendroglioma - genetics ; Oligodendroglioma - mortality ; Oligodendroglioma - pathology ; Priority Research Paper ; Prognosis ; Treatment Outcome</subject><ispartof>Oncotarget, 2017-05, Vol.8 (22), p.35523-35531</ispartof><rights>Copyright: © 2017 Holdhoff et al. 2017</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-6ca23d3f17d2ce0923dc92a2ffc0a6522912c9c75afde410ea23a742c04ba8423</citedby><cites>FETCH-LOGICAL-c356t-6ca23d3f17d2ce0923dc92a2ffc0a6522912c9c75afde410ea23a742c04ba8423</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482595/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482595/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28388591$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Holdhoff, Matthias</creatorcontrib><creatorcontrib>Cairncross, Gregory J</creatorcontrib><creatorcontrib>Kollmeyer, Thomas M</creatorcontrib><creatorcontrib>Zhang, Ming</creatorcontrib><creatorcontrib>Zhang, Peixin</creatorcontrib><creatorcontrib>Mehta, Minesh P</creatorcontrib><creatorcontrib>Werner-Wasik, Maria</creatorcontrib><creatorcontrib>Souhami, Luis</creatorcontrib><creatorcontrib>Bahary, Jean-Paul</creatorcontrib><creatorcontrib>Kwok, Young</creatorcontrib><creatorcontrib>Hartford, Alan C</creatorcontrib><creatorcontrib>Chakravarti, Arnab</creatorcontrib><creatorcontrib>Yegnasubramanian, Srinivasan</creatorcontrib><creatorcontrib>Vogelstein, Bert</creatorcontrib><creatorcontrib>Papadopoulos, Nickolas</creatorcontrib><creatorcontrib>Kinzler, Kenneth</creatorcontrib><creatorcontrib>Jenkins, Robert B</creatorcontrib><creatorcontrib>Bettegowda, Chetan</creatorcontrib><title>Genetic landscape of extreme responders with anaplastic oligodendroglioma</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>The NRG Oncology RTOG 9402 trial showed significant survival benefit in patients with 1p/19q co-deleted anaplastic oligodendrogliomas (AO) who received both radiation (RT) and chemotherapy (PCV regimen) versus RT alone. Substantial separation of the survival curves was only seen after 7.3 years. We aimed to determine whether there are specific genetic alterations that distinguish co-deleted AO patients who benefit from the addition of PCV from those who do not.
We performed whole exome sequencing on matched tumor and normal DNA from all available short-term (STS) and long-term survivors (LTS) who received RT+PCV. hTERT status and rs55705857 genotypes (G-allele) were analyzed in both cohorts.
Six STS (survival of <7.3y) and 7 LTS (survival of ≥7.3y and no progression) had sufficient material for analysis. There was no significant difference between the groups regarding age, performance status and extent of resection. On average, STS had 7 and LTS 4 mutations. Most common mutations in STS vs. LTS were: IDH1 (67 vs. 86%), CIC (50 vs. 71%) and FUBP1 (17 vs. 71%). The hTERT promoter was mutated in 83% STS and 86% LTS. Genotyping of rs55705857 showed a higher prevalence of G allele carriers in LTS than STS (43 vs. 17%).
These findings confirm that IDH, CIC, FUBP1 mutations and rs55705857 genotype are common in AO. 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Cairncross, Gregory J ; Kollmeyer, Thomas M ; Zhang, Ming ; Zhang, Peixin ; Mehta, Minesh P ; Werner-Wasik, Maria ; Souhami, Luis ; Bahary, Jean-Paul ; Kwok, Young ; Hartford, Alan C ; Chakravarti, Arnab ; Yegnasubramanian, Srinivasan ; Vogelstein, Bert ; Papadopoulos, Nickolas ; Kinzler, Kenneth ; Jenkins, Robert B ; Bettegowda, Chetan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-6ca23d3f17d2ce0923dc92a2ffc0a6522912c9c75afde410ea23a742c04ba8423</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Alleles</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Biomarkers, Tumor</topic><topic>Brain Neoplasms - drug therapy</topic><topic>Brain Neoplasms - genetics</topic><topic>Brain Neoplasms - mortality</topic><topic>Brain Neoplasms - pathology</topic><topic>Chromosome Aberrations</topic><topic>Chromosomes, Human, Pair 1</topic><topic>Chromosomes, Human, Pair 19</topic><topic>Female</topic><topic>Genetic Variation</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Neoplasm Grading</topic><topic>Oligodendroglioma - drug therapy</topic><topic>Oligodendroglioma - genetics</topic><topic>Oligodendroglioma - mortality</topic><topic>Oligodendroglioma - pathology</topic><topic>Priority Research Paper</topic><topic>Prognosis</topic><topic>Treatment Outcome</topic><toplevel>online_resources</toplevel><creatorcontrib>Holdhoff, Matthias</creatorcontrib><creatorcontrib>Cairncross, Gregory J</creatorcontrib><creatorcontrib>Kollmeyer, Thomas M</creatorcontrib><creatorcontrib>Zhang, Ming</creatorcontrib><creatorcontrib>Zhang, Peixin</creatorcontrib><creatorcontrib>Mehta, Minesh P</creatorcontrib><creatorcontrib>Werner-Wasik, Maria</creatorcontrib><creatorcontrib>Souhami, Luis</creatorcontrib><creatorcontrib>Bahary, Jean-Paul</creatorcontrib><creatorcontrib>Kwok, Young</creatorcontrib><creatorcontrib>Hartford, Alan C</creatorcontrib><creatorcontrib>Chakravarti, Arnab</creatorcontrib><creatorcontrib>Yegnasubramanian, Srinivasan</creatorcontrib><creatorcontrib>Vogelstein, Bert</creatorcontrib><creatorcontrib>Papadopoulos, Nickolas</creatorcontrib><creatorcontrib>Kinzler, Kenneth</creatorcontrib><creatorcontrib>Jenkins, Robert B</creatorcontrib><creatorcontrib>Bettegowda, Chetan</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oncotarget</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Holdhoff, Matthias</au><au>Cairncross, Gregory J</au><au>Kollmeyer, Thomas M</au><au>Zhang, Ming</au><au>Zhang, Peixin</au><au>Mehta, Minesh P</au><au>Werner-Wasik, Maria</au><au>Souhami, Luis</au><au>Bahary, Jean-Paul</au><au>Kwok, Young</au><au>Hartford, Alan C</au><au>Chakravarti, Arnab</au><au>Yegnasubramanian, Srinivasan</au><au>Vogelstein, Bert</au><au>Papadopoulos, Nickolas</au><au>Kinzler, Kenneth</au><au>Jenkins, Robert B</au><au>Bettegowda, Chetan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic landscape of extreme responders with anaplastic oligodendroglioma</atitle><jtitle>Oncotarget</jtitle><addtitle>Oncotarget</addtitle><date>2017-05-30</date><risdate>2017</risdate><volume>8</volume><issue>22</issue><spage>35523</spage><epage>35531</epage><pages>35523-35531</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><abstract>The NRG Oncology RTOG 9402 trial showed significant survival benefit in patients with 1p/19q co-deleted anaplastic oligodendrogliomas (AO) who received both radiation (RT) and chemotherapy (PCV regimen) versus RT alone. Substantial separation of the survival curves was only seen after 7.3 years. We aimed to determine whether there are specific genetic alterations that distinguish co-deleted AO patients who benefit from the addition of PCV from those who do not.
We performed whole exome sequencing on matched tumor and normal DNA from all available short-term (STS) and long-term survivors (LTS) who received RT+PCV. hTERT status and rs55705857 genotypes (G-allele) were analyzed in both cohorts.
Six STS (survival of <7.3y) and 7 LTS (survival of ≥7.3y and no progression) had sufficient material for analysis. There was no significant difference between the groups regarding age, performance status and extent of resection. On average, STS had 7 and LTS 4 mutations. Most common mutations in STS vs. LTS were: IDH1 (67 vs. 86%), CIC (50 vs. 71%) and FUBP1 (17 vs. 71%). The hTERT promoter was mutated in 83% STS and 86% LTS. Genotyping of rs55705857 showed a higher prevalence of G allele carriers in LTS than STS (43 vs. 17%).
These findings confirm that IDH, CIC, FUBP1 mutations and rs55705857 genotype are common in AO. No distinct genetic signature was identified to differentiate STS and LTS.</abstract><cop>United States</cop><pub>Impact Journals LLC</pub><pmid>28388591</pmid><doi>10.18632/oncotarget.16773</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Alleles Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biomarkers, Tumor Brain Neoplasms - drug therapy Brain Neoplasms - genetics Brain Neoplasms - mortality Brain Neoplasms - pathology Chromosome Aberrations Chromosomes, Human, Pair 1 Chromosomes, Human, Pair 19 Female Genetic Variation Humans Male Middle Aged Mutation Neoplasm Grading Oligodendroglioma - drug therapy Oligodendroglioma - genetics Oligodendroglioma - mortality Oligodendroglioma - pathology Priority Research Paper Prognosis Treatment Outcome |
| title | Genetic landscape of extreme responders with anaplastic oligodendroglioma |
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