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Comparative genomic analysis reveals bilateral breast cancers are genetically independent.
Oncotarget 2015; 6(31):31820-9O

Abstract

Bilateral breast cancer (BBC) poses a major challenge for oncologists because of the cryptic relationship between the two lesions. The purpose of this study was to determine the origin of the contralateral breast cancer (either dependent or independent of the index tumor). Here, we used ultra-deep whole-exome sequencing and array comparative genomic hybridization (aCGH) to study four paired samples of BBCs with different tumor subtypes and time intervals between the developments of each tumor. We used two paired primary breast tumors and corresponding metastatic liver lesions as the control. We tested the origin independent nature of BBC in three ways: mutational concordance, mutational signature clustering, and clonality analysis using copy number profiles. We found that the paired BBC samples had near-zero concordant mutation rates, which were much lower than those of the paired primary/metastasis samples. The results of a mutational signature analysis also suggested that BBCs are independent of one another. A clonality analysis using aCGH data further revealed that paired BBC samples was clonally independent, in contrast to clonal related origin found for paired primary/metastasis samples. Our preliminary findings show that BBCs in Han Chinese women are origin independent and thus should be treated separately.

Authors+Show Affiliations

Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.BGI-Shenzhen, Shenzhen, China. Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong.Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.BGI-Shenzhen, Shenzhen, China.BGI-Shenzhen, Shenzhen, China.Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.

Pub Type(s)

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

Language

eng

PubMed ID

26378809

Citation

Song, Fangfang, et al. "Comparative Genomic Analysis Reveals Bilateral Breast Cancers Are Genetically Independent." Oncotarget, vol. 6, no. 31, 2015, pp. 31820-9.
Song F, Li X, Song F, et al. Comparative genomic analysis reveals bilateral breast cancers are genetically independent. Oncotarget. 2015;6(31):31820-9.
Song, F., Li, X., Song, F., Zhao, Y., Li, H., Zheng, H., ... Chen, K. (2015). Comparative genomic analysis reveals bilateral breast cancers are genetically independent. Oncotarget, 6(31), pp. 31820-9. doi:10.18632/oncotarget.5569.
Song F, et al. Comparative Genomic Analysis Reveals Bilateral Breast Cancers Are Genetically Independent. Oncotarget. 2015 Oct 13;6(31):31820-9. PubMed PMID: 26378809.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative genomic analysis reveals bilateral breast cancers are genetically independent. AU - Song,Fangfang, AU - Li,Xiangchun, AU - Song,Fengju, AU - Zhao,Yanrui, AU - Li,Haixin, AU - Zheng,Hong, AU - Gao,Zhibo, AU - Wang,Jun, AU - Zhang,Wei, AU - Chen,Kexin, PY - 2015/05/14/received PY - 2015/08/14/accepted PY - 2015/9/18/entrez PY - 2015/9/18/pubmed PY - 2016/8/24/medline KW - array comparative genomic hybridization KW - bilateral breast cancer KW - clonality KW - exome sequencing KW - genetic concordance SP - 31820 EP - 9 JF - Oncotarget JO - Oncotarget VL - 6 IS - 31 N2 - Bilateral breast cancer (BBC) poses a major challenge for oncologists because of the cryptic relationship between the two lesions. The purpose of this study was to determine the origin of the contralateral breast cancer (either dependent or independent of the index tumor). Here, we used ultra-deep whole-exome sequencing and array comparative genomic hybridization (aCGH) to study four paired samples of BBCs with different tumor subtypes and time intervals between the developments of each tumor. We used two paired primary breast tumors and corresponding metastatic liver lesions as the control. We tested the origin independent nature of BBC in three ways: mutational concordance, mutational signature clustering, and clonality analysis using copy number profiles. We found that the paired BBC samples had near-zero concordant mutation rates, which were much lower than those of the paired primary/metastasis samples. The results of a mutational signature analysis also suggested that BBCs are independent of one another. A clonality analysis using aCGH data further revealed that paired BBC samples was clonally independent, in contrast to clonal related origin found for paired primary/metastasis samples. Our preliminary findings show that BBCs in Han Chinese women are origin independent and thus should be treated separately. SN - 1949-2553 UR - https://www.unboundmedicine.com/medline/citation/26378809/Comparative_genomic_analysis_reveals_bilateral_breast_cancers_are_genetically_independent_ L2 - http://www.impactjournals.com/oncotarget/misc/linkedout.php?pii=5569 DB - PRIME DP - Unbound Medicine ER -