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Comparative analysis of the EGFR, HER2, c-MYC, and MET variations in colorectal cancer determined by three different measures: gene copy number gain, amplification status and the 2013 ASCO/CAP guideline criterion for HER2 testing of breast cancer

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dc.contributor.authorKwak, Yoonjin-
dc.contributor.authorYun, Sumi-
dc.contributor.authorNam, Soo Kyung-
dc.contributor.authorSeo, An Na-
dc.contributor.authorLee, Kyu Sang-
dc.contributor.authorShin, Eun-
dc.contributor.authorOh, Heung-Kwon-
dc.contributor.authorKim, Duck Woo-
dc.contributor.authorKang, Sung Bum-
dc.contributor.authorKim, Woo Ho-
dc.contributor.authorLee, Hye Seung-
dc.date.accessioned2017-11-02T07:12:48Z-
dc.date.available2017-11-02T16:13:46Z-
dc.date.issued2017-08-01-
dc.identifier.citationJournal of Translational Medicine, 15(1):167ko_KR
dc.identifier.issn1479-5876-
dc.identifier.urihttps://hdl.handle.net/10371/138305-
dc.descriptionAbbreviations
GCN: gene copy number; CRC: colorectal cancer; EGFR: human epidermal growth factor receptor; HER2: human epidermal growth receptor 2; SISH: silver in situ hybridization; PFS: progression-free survival; OS: overall survival; TMA: tissue microarray; ASCO/CAP: American Society of Clinical Oncology/College
of American Pathologists; MSI: microsatellite instability.
ko_KR
dc.description.abstractAbstract

Background
The purpose of this study was to explore gene copy number (GCN) variation of EGFR, HER2, c-MYC, and MET in patients with primary colorectal cancer (CRC).

Methods
Dual-colour silver-enhanced in situ hybridization was performed in tissue samples of 334 primary CRC patients. The amplification status (GCN ratio ≥2) and GCN gain (average GCN ≥4) data for the EGFR, HER2, c-MYC and MET genes were obtained. GCN variation was also assessed by the criterion of the 2013 ASCO/CAP guidelines for HER2 testing.

Results
Amplification of EGFR, HER2, c-MYC and MET was detected in 8 (2.4%), 20 (6.0%), 29 (8.7%), and 14 (4.2%) patients, respectively. Of 66 patients with at least one amplified gene, five exhibited co-amplification of genes studied (HER2-MET co-amplification: two patients; HER2-c-MYC co-amplification: two patients; EGFR-c-MYC co-amplification: one patient). There were 109 patients with GCN gains of one or more genes (EGFR: 11/334, HER2: 29/334, c-MYC; 60/334, MET: 48/334) and 32.1% (35/109) had multiple GCN gains. When each GCN was assessed by the criterion of the ASCO/CAP 2013 guideline for HER2 testing, 116 people showed positive or equivocal results for one or more genes. The cumulative amplification status had no association with patients outcome. However, the cumulative results of the GCN gain and GCN status determined according to the ASCO/CAP guideline had a significant prognostic correlation in the univariate analysis (P values of 0.006 and 0.022, respectively). In the multivariate analysis, GCN gain and GCN status were independent prognostic factors (P values of 0.010 and 0.017, respectively).

Conclusions
In this study, we evaluated GCN variation of four genes in a large sample of Korean CRC patients. The amplification status was not related to patient outcome. However, the GCN gain and GCN status according to the ASCO/CAP 2013 guideline were independent prognostic factors.
ko_KR
dc.description.sponsorshipThis study was funded through a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant Number: HI14C1813).ko_KR
dc.language.isoenko_KR
dc.publisherBioMed Centralko_KR
dc.subjectGene copy number variationko_KR
dc.subjectEGFRko_KR
dc.subjectHER2ko_KR
dc.subjectc-MYCko_KR
dc.subjectMETko_KR
dc.subjectColorectal cancerko_KR
dc.titleComparative analysis of the EGFR, HER2, c-MYC, and MET variations in colorectal cancer determined by three different measures: gene copy number gain, amplification status and the 2013 ASCO/CAP guideline criterion for HER2 testing of breast cancerko_KR
dc.typeArticleko_KR
dc.contributor.AlternativeAuthor곽윤진-
dc.contributor.AlternativeAuthor윤수미-
dc.contributor.AlternativeAuthor남수경-
dc.contributor.AlternativeAuthor서안나-
dc.contributor.AlternativeAuthor이규상-
dc.contributor.AlternativeAuthor신은-
dc.contributor.AlternativeAuthor오흥권-
dc.contributor.AlternativeAuthor김덕우-
dc.contributor.AlternativeAuthor강성범-
dc.contributor.AlternativeAuthor김우호-
dc.contributor.AlternativeAuthor이혜승-
dc.identifier.doi10.1186/s12967-017-1265-x-
dc.language.rfc3066en-
dc.rights.holderThe Author(s)-
dc.date.updated2017-10-03T16:52:22Z-
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Pathology (병리학전공)Journal Papers (저널논문_병리학전공)
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