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c-MYC Copy-Number Gain Is an Independent Prognostic Factor in Patients with Colorectal Cancer.
PLoS One. 2015; 10(10):e0139727.Plos

Abstract

BACKGROUND

The aim of this study was to determine the incidence and clinicopathological significance of c-MYC gene copy-number (GCN) gain in patients with primary colorectal cancer (CRC).

METHODS

The c-MYC GCN was investigated in 367 consecutive CRC patients (cohort 1) by using dual-color silver in situ hybridization. Additionally, to evaluate regional heterogeneity, we examined CRC tissue from 3 sites including the primary cancer, distant metastasis, and lymph-node metastasis in 152 advanced CRC patients (cohort 2). KRAS exons 2 and 3 were investigated for mutations.

RESULTS

In cohort 1, c-MYC gene amplification, defined by a c-MYC:centromere of chromosome 8 ratio ≥ 2.0, was detected in 31 (8.4%) of 367 patients. A c-MYC GCN gain, defined by ≥ 4.0 c-MYC copies/nucleus, was found in 63 (17.2%) patients and was associated with poor prognosis (P = 0.015). Multivariate Cox regression analysis showed that the hazard ratio for c-MYC GCN gain was 2.35 (95% confidence interval, 1.453-3.802; P < 0.001). In a subgroup of stage II-III CRC patients, c-MYC GCN gain was significantly associated with poor prognosis by univariate (P = 0.034) and multivariate (P = 0.040) analyses. c-MYC protein overexpression was observed in 201 (54.8%) out of 367 patients and weakly correlated with c-MYC GCN gain (ρ, 0.211). In cohort 2, the c-MYC genetic status was heterogenous in advanced CRC patients. Discordance between GCN gain in the primary tumor and either distant or lymph-node metastasis was 25.7% and 30.4%, respectively. A similar frequency for c-MYC GCN gain and amplification was observed in CRC patients with both wild-type and mutated KRAS.

CONCLUSIONS

c-MYC GCN gain was an independent factor for poor prognosis in consecutive CRC patients and in the stage II-III subgroup. Our findings indicate that the status of c-MYC may be helpful in predicting the patients' outcome and for managing CRC patients.

Authors+Show Affiliations

Department of Pathology, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea.Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.Department of Pathology, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea.Department of Surgery, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea.Department of Surgery, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea.Department of Pathology, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea; Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.Department of Pathology, Seoul National University Bundang Hospital, Seongnam-si, Republic of Korea.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26426996

Citation

Lee, Kyu Sang, et al. "C-MYC Copy-Number Gain Is an Independent Prognostic Factor in Patients With Colorectal Cancer." PloS One, vol. 10, no. 10, 2015, pp. e0139727.
Lee KS, Kwak Y, Nam KH, et al. C-MYC Copy-Number Gain Is an Independent Prognostic Factor in Patients with Colorectal Cancer. PLoS ONE. 2015;10(10):e0139727.
Lee, K. S., Kwak, Y., Nam, K. H., Kim, D. W., Kang, S. B., Choe, G., Kim, W. H., & Lee, H. S. (2015). C-MYC Copy-Number Gain Is an Independent Prognostic Factor in Patients with Colorectal Cancer. PloS One, 10(10), e0139727. https://doi.org/10.1371/journal.pone.0139727
Lee KS, et al. C-MYC Copy-Number Gain Is an Independent Prognostic Factor in Patients With Colorectal Cancer. PLoS ONE. 2015;10(10):e0139727. PubMed PMID: 26426996.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - c-MYC Copy-Number Gain Is an Independent Prognostic Factor in Patients with Colorectal Cancer. AU - Lee,Kyu Sang, AU - Kwak,Yoonjin, AU - Nam,Kyung Han, AU - Kim,Duck-Woo, AU - Kang,Sung-Bum, AU - Choe,Gheeyoung, AU - Kim,Woo Ho, AU - Lee,Hye Seung, Y1 - 2015/10/01/ PY - 2015/05/24/received PY - 2015/09/15/accepted PY - 2015/10/2/entrez PY - 2015/10/2/pubmed PY - 2016/6/15/medline SP - e0139727 EP - e0139727 JF - PloS one JO - PLoS ONE VL - 10 IS - 10 N2 - BACKGROUND: The aim of this study was to determine the incidence and clinicopathological significance of c-MYC gene copy-number (GCN) gain in patients with primary colorectal cancer (CRC). METHODS: The c-MYC GCN was investigated in 367 consecutive CRC patients (cohort 1) by using dual-color silver in situ hybridization. Additionally, to evaluate regional heterogeneity, we examined CRC tissue from 3 sites including the primary cancer, distant metastasis, and lymph-node metastasis in 152 advanced CRC patients (cohort 2). KRAS exons 2 and 3 were investigated for mutations. RESULTS: In cohort 1, c-MYC gene amplification, defined by a c-MYC:centromere of chromosome 8 ratio ≥ 2.0, was detected in 31 (8.4%) of 367 patients. A c-MYC GCN gain, defined by ≥ 4.0 c-MYC copies/nucleus, was found in 63 (17.2%) patients and was associated with poor prognosis (P = 0.015). Multivariate Cox regression analysis showed that the hazard ratio for c-MYC GCN gain was 2.35 (95% confidence interval, 1.453-3.802; P < 0.001). In a subgroup of stage II-III CRC patients, c-MYC GCN gain was significantly associated with poor prognosis by univariate (P = 0.034) and multivariate (P = 0.040) analyses. c-MYC protein overexpression was observed in 201 (54.8%) out of 367 patients and weakly correlated with c-MYC GCN gain (ρ, 0.211). In cohort 2, the c-MYC genetic status was heterogenous in advanced CRC patients. Discordance between GCN gain in the primary tumor and either distant or lymph-node metastasis was 25.7% and 30.4%, respectively. A similar frequency for c-MYC GCN gain and amplification was observed in CRC patients with both wild-type and mutated KRAS. CONCLUSIONS: c-MYC GCN gain was an independent factor for poor prognosis in consecutive CRC patients and in the stage II-III subgroup. Our findings indicate that the status of c-MYC may be helpful in predicting the patients' outcome and for managing CRC patients. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/26426996/c_MYC_Copy_Number_Gain_Is_an_Independent_Prognostic_Factor_in_Patients_with_Colorectal_Cancer_ L2 - http://dx.plos.org/10.1371/journal.pone.0139727 DB - PRIME DP - Unbound Medicine ER -