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MYC overexpression and poor prognosis in sporadic breast cancer with BRCA1 deficiency.
Tumour Biol. 2013 Dec; 34(6):3945-58.TB

Abstract

Breast cancer is a complex disease; the molecular mechanisms involved in sporadic breast carcinogenesis remain to be elucidated. The present study aimed to explore the deficiency of breast cancer susceptibility gene 1 (BRCA1), including protein loss expression, promoter hypermethylation and gene copy deletion, its correlationship with other tumor markers expression (TP53, MYC, etc.), and clinical significance in sporadic breast cancer. BRCA1 protein expression was negative in 226 of 374 (60.4%) cases of this study. Cases negative for BRCA1 protein were more often with pathological tumor-node-metastasis stage III, positive for lymph node metastasis and MYC overexpression than BRCA1-positive tumors. BRCA1 hypermethylation was detected in 16.4% (31 of 189) breast cancers, which correlated with BRCA1 negative, ER negative, MYC overexpression, and triple-negative phenotype. In addition, the percentage of cells with BRCA1 gene copy deletion was significantly increased in BRCA1-methylated tumors. Kaplan-Meier survival analysis showed that patients with BRCA1-negative expression showed a worse overall survival (OS) than those with BRCA1-positive expression, and patients with BRCA1-methylated tumors had a significantly worse disease-free survival than did patients with unmethylated tumors. Furthermore, BRCA1 hypermethylation showed an inverse association with OS in LN-positive or p53-negative subgroup patients. Importantly, uni- and multivariate Cox regression analyses revealed that BRCA1 was an independent prognostic indicator of OS in sporadic breast cancer. Thus, we found MYC overexpression and poor prognosis in sporadic breast cancer with BRCA1 deficiency. The targeting of BRCA1 deficiency in combination with MYC-pathways inhibitors may provide a promising strategy for sporadic breast cancer care, the triple-negative subtype in particular.

Authors+Show Affiliations

Department of Pharmacology, College of Pharmaceutical Sciences, China Medical University, Shenyang, 110001, Liaoning, People's Republic of China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

23860775

Citation

Ren, Jie, et al. "MYC Overexpression and Poor Prognosis in Sporadic Breast Cancer With BRCA1 Deficiency." Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine, vol. 34, no. 6, 2013, pp. 3945-58.
Ren J, Jin F, Yu Z, et al. MYC overexpression and poor prognosis in sporadic breast cancer with BRCA1 deficiency. Tumour Biol. 2013;34(6):3945-58.
Ren, J., Jin, F., Yu, Z., Zhao, L., Wang, L., Bai, X., Zhao, H., Yao, W., Mi, X., Wang, E., Olopade, O. I., & Wei, M. (2013). MYC overexpression and poor prognosis in sporadic breast cancer with BRCA1 deficiency. Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine, 34(6), 3945-58. https://doi.org/10.1007/s13277-013-0983-9
Ren J, et al. MYC Overexpression and Poor Prognosis in Sporadic Breast Cancer With BRCA1 Deficiency. Tumour Biol. 2013;34(6):3945-58. PubMed PMID: 23860775.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MYC overexpression and poor prognosis in sporadic breast cancer with BRCA1 deficiency. AU - Ren,Jie, AU - Jin,Feng, AU - Yu,Zhaojin, AU - Zhao,Lin, AU - Wang,Lin, AU - Bai,Xuefeng, AU - Zhao,Haishan, AU - Yao,Weifan, AU - Mi,Xiaoyi, AU - Wang,Enhua, AU - Olopade,Olufunmilayo I, AU - Wei,Minjie, Y1 - 2013/07/17/ PY - 2013/05/10/received PY - 2013/06/26/accepted PY - 2013/7/18/entrez PY - 2013/7/19/pubmed PY - 2014/2/22/medline SP - 3945 EP - 58 JF - Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine JO - Tumour Biol. VL - 34 IS - 6 N2 - Breast cancer is a complex disease; the molecular mechanisms involved in sporadic breast carcinogenesis remain to be elucidated. The present study aimed to explore the deficiency of breast cancer susceptibility gene 1 (BRCA1), including protein loss expression, promoter hypermethylation and gene copy deletion, its correlationship with other tumor markers expression (TP53, MYC, etc.), and clinical significance in sporadic breast cancer. BRCA1 protein expression was negative in 226 of 374 (60.4%) cases of this study. Cases negative for BRCA1 protein were more often with pathological tumor-node-metastasis stage III, positive for lymph node metastasis and MYC overexpression than BRCA1-positive tumors. BRCA1 hypermethylation was detected in 16.4% (31 of 189) breast cancers, which correlated with BRCA1 negative, ER negative, MYC overexpression, and triple-negative phenotype. In addition, the percentage of cells with BRCA1 gene copy deletion was significantly increased in BRCA1-methylated tumors. Kaplan-Meier survival analysis showed that patients with BRCA1-negative expression showed a worse overall survival (OS) than those with BRCA1-positive expression, and patients with BRCA1-methylated tumors had a significantly worse disease-free survival than did patients with unmethylated tumors. Furthermore, BRCA1 hypermethylation showed an inverse association with OS in LN-positive or p53-negative subgroup patients. Importantly, uni- and multivariate Cox regression analyses revealed that BRCA1 was an independent prognostic indicator of OS in sporadic breast cancer. Thus, we found MYC overexpression and poor prognosis in sporadic breast cancer with BRCA1 deficiency. The targeting of BRCA1 deficiency in combination with MYC-pathways inhibitors may provide a promising strategy for sporadic breast cancer care, the triple-negative subtype in particular. SN - 1423-0380 UR - https://www.unboundmedicine.com/medline/citation/23860775/MYC_overexpression_and_poor_prognosis_in_sporadic_breast_cancer_with_BRCA1_deficiency_ L2 - https://link.springer.com/article/10.1007/s13277-013-0983-9 DB - PRIME DP - Unbound Medicine ER -