Cited 41 times in
Genetic alterations and their clinical implications in gastric cancer peritoneal carcinomatosis revealed by whole-exome sequencing of malignant ascites
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 김태수 | - |
dc.contributor.author | 정현철 | - |
dc.contributor.author | 김효송 | - |
dc.contributor.author | 박규현 | - |
dc.contributor.author | 박준용 | - |
dc.contributor.author | 라선영 | - |
dc.contributor.author | 권우선 | - |
dc.date.accessioned | 2017-02-27T08:07:16Z | - |
dc.date.available | 2017-02-27T08:07:16Z | - |
dc.date.issued | 2016 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/147093 | - |
dc.description.abstract | Peritoneal carcinomatosis accompanied by malignant ascites is a major cause of death of advanced gastric cancer (GC). To comprehensively characterize the underlying genomic events involved in GC peritoneal carcinomatosis, we analyzed whole-exome sequences of normal gastric tissues, primary tumors, and malignant ascites from eight GC patients. We identified a unique mutational signature biased toward C-to-A substitutions in malignant ascites. In contrast, the patients who received treatment of adjuvant chemotherapy showed a high rate of C-to-T substitutions along with hypermutation in malignant ascites. Comparative analysis revealed several candidate mutations for GC peritoneal carcinomatosis: recurrent mutations in COL4A6, INTS2, and PTPN13; mutations in druggable genes including TEP1, PRKCD, BRAF, ERBB4, PIK3CA, HDAC9, FYN, FASN, BIRC2, FLT3, ROCK1, CD22, and PIK3C2B; and mutations in metastasis-associated genes including TNFSF12, L1CAM, DIAPH3, ROCK1, TGFBR1, MYO9B, NR4A1, and RHOA. Notably, gene ontology analysis revealed the significant enrichment of mutations in the Rho-ROCK signaling pathway-associated biological processes in malignant ascites. At least four of the eight patients acquired somatic mutations in the Rho-ROCK pathway components, suggesting the possible relevance of this pathway to GC peritoneal carcinomatosis. These results provide a genome-wide molecular understanding of GC peritoneal carcinomatosis and its clinical implications, thereby facilitating the development of effective therapeutics. | - |
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 | Adult | - |
dc.subject.MESH | Aged | - |
dc.subject.MESH | Ascites/genetics* | - |
dc.subject.MESH | Biomarkers, Tumor/genetics* | - |
dc.subject.MESH | Case-Control Studies | - |
dc.subject.MESH | Exome/genetics* | - |
dc.subject.MESH | Female | - |
dc.subject.MESH | Follow-Up Studies | - |
dc.subject.MESH | Genome, Human* | - |
dc.subject.MESH | High-Throughput Nucleotide Sequencing/methods | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Male | - |
dc.subject.MESH | Middle Aged | - |
dc.subject.MESH | Mutation/genetics* | - |
dc.subject.MESH | Neoplasm Staging | - |
dc.subject.MESH | Peritoneal Neoplasms/genetics | - |
dc.subject.MESH | Peritoneal Neoplasms/secondary* | - |
dc.subject.MESH | Prognosis | - |
dc.subject.MESH | Retrospective Studies | - |
dc.subject.MESH | Stomach Neoplasms/genetics | - |
dc.subject.MESH | Stomach Neoplasms/pathology* | - |
dc.title | Genetic alterations and their clinical implications in gastric cancer peritoneal carcinomatosis revealed by whole-exome sequencing of malignant ascites | - |
dc.type | Article | - |
dc.publisher.location | United States | - |
dc.contributor.college | College of Medicine | - |
dc.contributor.department | Dept. of Internal Medicine | - |
dc.contributor.googleauthor | Byungho Lim | - |
dc.contributor.googleauthor | Chan Kim | - |
dc.contributor.googleauthor | Jeong-Hwan Kim | - |
dc.contributor.googleauthor | Woo Sun Kwon | - |
dc.contributor.googleauthor | Won Seok Lee | - |
dc.contributor.googleauthor | Jeong Min Kim | - |
dc.contributor.googleauthor | Jun Yong Park | - |
dc.contributor.googleauthor | Hyo Song Kim | - |
dc.contributor.googleauthor | Kyu Hyun Park | - |
dc.contributor.googleauthor | Tae Soo Kim | - |
dc.contributor.googleauthor | Jong-Lyul Park | - |
dc.contributor.googleauthor | Hyun Cheol Chung | - |
dc.contributor.googleauthor | Sun Young Rha | - |
dc.contributor.googleauthor | Seon-Young Kim | - |
dc.identifier.doi | 10.18632/oncotarget.6977 | - |
dc.contributor.localId | A04549 | - |
dc.contributor.localId | A03773 | - |
dc.contributor.localId | A01202 | - |
dc.contributor.localId | A04566 | - |
dc.contributor.localId | A01675 | - |
dc.contributor.localId | A01316 | - |
dc.relation.journalcode | J02421 | - |
dc.identifier.eissn | 1949-2553 | - |
dc.identifier.pmid | 26811494 | - |
dc.subject.keyword | exome sequencing | - |
dc.subject.keyword | gastric cancer | - |
dc.subject.keyword | malignant ascites | - |
dc.subject.keyword | peritoneal carcinomatosis | - |
dc.subject.keyword | somatic mutation | - |
dc.contributor.alternativeName | Kim, Tae Soo | - |
dc.contributor.alternativeName | Chung, Hyun Cheol | - |
dc.contributor.alternativeName | Kim, Hyo Song | - |
dc.contributor.alternativeName | Park, Kyu Hyun | - |
dc.contributor.alternativeName | Park, Jun Yong | - |
dc.contributor.alternativeName | Rha, Sun Young | - |
dc.contributor.affiliatedAuthor | Kim, Tae Soo | - |
dc.contributor.affiliatedAuthor | Chung, Hyun Cheol | - |
dc.contributor.affiliatedAuthor | Kim, Hyo Song | - |
dc.contributor.affiliatedAuthor | Park, Kyu Hyun | - |
dc.contributor.affiliatedAuthor | Park, Jun Yong | - |
dc.contributor.affiliatedAuthor | Rha, Sun Young | - |
dc.citation.volume | 7 | - |
dc.citation.number | 7 | - |
dc.citation.startPage | 8055 | - |
dc.citation.endPage | 8066 | - |
dc.identifier.bibliographicCitation | ONCOTARGET, Vol.7(7) : 8055-8066, 2016 | - |
dc.date.modified | 2017-02-24 | - |
dc.identifier.rimsid | 47125 | - |
dc.type.rims | ART | - |
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