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Next-generation sequencing reveals somatic mutations that confer exceptional response to everolimus
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 김상우 | - |
dc.contributor.author | 김현기 | - |
dc.contributor.author | 김혜련 | - |
dc.contributor.author | 김효송 | - |
dc.contributor.author | 박형순 | - |
dc.contributor.author | 이민구 | - |
dc.contributor.author | 임선민 | - |
dc.contributor.author | 정현철 | - |
dc.contributor.author | 조병철 | - |
dc.contributor.author | 김소라 | - |
dc.contributor.author | 양인석 | - |
dc.date.accessioned | 2017-10-26T07:38:33Z | - |
dc.date.available | 2017-10-26T07:38:33Z | - |
dc.date.issued | 2016 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/152318 | - |
dc.description.abstract | BACKGROUND: Given the modest responses to everolimus, a mTOR inhibitor, in multiple tumor types, there is a pressing need to identify predictive biomarkers for this drug. Using targeted ultra-deep sequencing, we aimed to explore genomic alterations that confer extreme sensitivity to everolimus. RESULTS: We collected formalin-fixed paraffin-embedded tumor/normal pairs from 39 patients (22 with exceptional clinical benefit, 17 with no clinical benefit) who were treated with everolimus across various tumor types (13 gastric cancers, 15 renal cell carcinomas, 2 thyroid cancers, 2 head and neck cancer, and 7 sarcomas). Ion AmpliSeqTM Comprehensive Cancer Panel was used to identify alterations across all exons of 409 target genes. Tumors were sequenced to a median coverage of 552x. Cancer genomes are characterized by 219 somatic single-nucleotide variants (181 missense, 9 nonsense, 7 splice-site) and 22 frameshift insertions/deletions, with a median of 2.1 mutations per Mb (0 to 12.4 mutations per Mb). Overall, genomic alterations with activating effect on mTOR signaling were identified in 10 of 22 (45%) patients with clinical benefit and these include MTOR, TSC1, TSC2, NF1, PIK3CA and PIK3CG mutations. Recurrently mutated genes in chromatin remodeling genes (BAP1; n = 2, 12%) and receptor tyrosine kinase signaling (FGFR4; n = 2, 12%) were noted only in patients without clinical benefit. CONCLUSIONS: Regardless of different cancer types, mTOR-pathway-activating mutations confer sensitivity to everolimus. Targeted sequencing of mTOR pathway genes facilitates identification of potential candidates for mTOR inhibitors. | - |
dc.description.statementOfResponsibility | open | - |
dc.format | application/pdf | - |
dc.language | English | - |
dc.publisher | Impact Journals | - |
dc.relation.isPartOf | ONCOTARGET | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Adenocarcinoma/drug therapy* | - |
dc.subject.MESH | Adult | - |
dc.subject.MESH | Aged | - |
dc.subject.MESH | Aged, 80 and over | - |
dc.subject.MESH | Antineoplastic Agents/therapeutic use* | - |
dc.subject.MESH | Carcinoma, Renal Cell/drug therapy | - |
dc.subject.MESH | Class I Phosphatidylinositol 3-Kinases | - |
dc.subject.MESH | Class Ib Phosphatidylinositol 3-Kinase/genetics | - |
dc.subject.MESH | Drug Resistance, Neoplasm/genetics* | - |
dc.subject.MESH | Everolimus/therapeutic use* | - |
dc.subject.MESH | Female | - |
dc.subject.MESH | Head and Neck Neoplasms/drug therapy | - |
dc.subject.MESH | High-Throughput Nucleotide Sequencing | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Kidney Neoplasms/drug therapy | - |
dc.subject.MESH | Lacrimal Apparatus/pathology* | - |
dc.subject.MESH | Male | - |
dc.subject.MESH | Middle Aged | - |
dc.subject.MESH | Mutation/genetics | - |
dc.subject.MESH | Neurofibromin 1/genetics* | - |
dc.subject.MESH | Phosphatidylinositol 3-Kinases/genetics | - |
dc.subject.MESH | Polymorphism, Single Nucleotide/genetics | - |
dc.subject.MESH | Sarcoma/drug therapy | - |
dc.subject.MESH | Stomach Neoplasms/drug therapy | - |
dc.subject.MESH | TOR Serine-Threonine Kinases/antagonists & inhibitors | - |
dc.subject.MESH | TOR Serine-Threonine Kinases/genetics* | - |
dc.subject.MESH | Thyroid Neoplasms/drug therapy | - |
dc.subject.MESH | Tumor Suppressor Protein p53/genetics* | - |
dc.subject.MESH | Tumor Suppressor Proteins/genetics | - |
dc.subject.MESH | Young Adult | - |
dc.title | Next-generation sequencing reveals somatic mutations that confer exceptional response to everolimus | - |
dc.type | Article | - |
dc.publisher.location | United States | - |
dc.contributor.college | College of Medicine | - |
dc.contributor.department | Dept. of Life Science | - |
dc.contributor.googleauthor | Sun Min Lim | - |
dc.contributor.googleauthor | Hyung Soon Park | - |
dc.contributor.googleauthor | Sangwoo Kim | - |
dc.contributor.googleauthor | Sora Kim | - |
dc.contributor.googleauthor | Siraj M. Ali | - |
dc.contributor.googleauthor | Joel R. Greenbowe | - |
dc.contributor.googleauthor | In Seok Yang | - |
dc.contributor.googleauthor | Nak-Jung Kwon | - |
dc.contributor.googleauthor | Jae Lyun Lee | - |
dc.contributor.googleauthor | Min-Hee Ryu | - |
dc.contributor.googleauthor | Jin-Hee Ahn | - |
dc.contributor.googleauthor | Jeeyun Lee | - |
dc.contributor.googleauthor | Min Goo Lee | - |
dc.contributor.googleauthor | Hyo Song Kim | - |
dc.contributor.googleauthor | Hyunki Kim | - |
dc.contributor.googleauthor | Hye Ryun Kim | - |
dc.contributor.googleauthor | Yong Wha Moon | - |
dc.contributor.googleauthor | Hyun Cheol Chung | - |
dc.contributor.googleauthor | Joo-Hang Kim | - |
dc.contributor.googleauthor | Yoon-Koo Kang | - |
dc.contributor.googleauthor | Byoung Chul Cho | - |
dc.identifier.doi | 10.18632/oncotarget.7234 | - |
dc.contributor.localId | A01108 | - |
dc.contributor.localId | A01166 | - |
dc.contributor.localId | A01202 | - |
dc.contributor.localId | A04576 | - |
dc.contributor.localId | A02781 | - |
dc.contributor.localId | A03369 | - |
dc.contributor.localId | A03773 | - |
dc.contributor.localId | A03822 | - |
dc.contributor.localId | A00612 | - |
dc.contributor.localId | A00524 | - |
dc.relation.journalcode | J02421 | - |
dc.identifier.eissn | 1949-2553 | - |
dc.identifier.pmid | 26859683 | - |
dc.subject.keyword | NF1 | - |
dc.subject.keyword | TSC1 | - |
dc.subject.keyword | everolimus | - |
dc.subject.keyword | mTOR | - |
dc.subject.keyword | next-generation sequencing | - |
dc.contributor.alternativeName | Kim, Sang Woo | - |
dc.contributor.alternativeName | Kim, Hyun Ki | - |
dc.contributor.alternativeName | Kim, Hye Ryun | - |
dc.contributor.alternativeName | Kim, Hyo Song | - |
dc.contributor.alternativeName | Park, Hyung Soon | - |
dc.contributor.alternativeName | Lee, Min Goo | - |
dc.contributor.alternativeName | Lim, Sun Min | - |
dc.contributor.alternativeName | Chung, Hyun Cheol | - |
dc.contributor.alternativeName | Cho, Byoung Chul | - |
dc.contributor.alternativeName | Kim, So Ra | - |
dc.contributor.affiliatedAuthor | Kim, Hyun Ki | - |
dc.contributor.affiliatedAuthor | Kim, Hye Ryun | - |
dc.contributor.affiliatedAuthor | Kim, Hyo Song | - |
dc.contributor.affiliatedAuthor | Park, Hyung Soon | - |
dc.contributor.affiliatedAuthor | Lee, Min Goo | - |
dc.contributor.affiliatedAuthor | Lim, Sun Min | - |
dc.contributor.affiliatedAuthor | Chung, Hyun Cheol | - |
dc.contributor.affiliatedAuthor | Cho, Byoung Chul | - |
dc.contributor.affiliatedAuthor | Kim, So Ra | - |
dc.contributor.affiliatedAuthor | Kim, Sang Woo | - |
dc.citation.volume | 7 | - |
dc.citation.number | 9 | - |
dc.citation.startPage | 10547 | - |
dc.citation.endPage | 10556 | - |
dc.identifier.bibliographicCitation | ONCOTARGET , Vol.7(9) : 10547-10556, 2016 | - |
dc.date.modified | 2017-10-24 | - |
dc.identifier.rimsid | 48053 | - |
dc.type.rims | ART | - |
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