Oncotarget

Research Papers:

Comparative genomic analysis reveals bilateral breast cancers are genetically independent

Fangfang Song, Xiangchun Li, Fengju Song, Yanrui Zhao, Haixin Li, Hong Zheng, Zhibo Gao, Jun Wang, Wei Zhang and Kexin Chen _

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Oncotarget. 2015; 6:31820-31829. https://doi.org/10.18632/oncotarget.5569

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Abstract

Fangfang Song1,*, Xiangchun Li2,3,*, Fengju Song1,*, Yanrui Zhao1, Haixin Li1, Hong Zheng1, Zhibo Gao2, Jun Wang2, Wei Zhang4 and Kexin Chen1

1 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, P.R. China

2 BGI-Shenzhen, Shenzhen, China

3 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

4 Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

* These authors have contributed equally to this work

Correspondence to:

Kexin Chen, email:

Wei Zhang, email:

Keywords: bilateral breast cancer, exome sequencing, array comparative genomic hybridization, clonality, genetic concordance

Received: May 14, 2015 Accepted: August 14, 2015 Published: September 10, 2015

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.


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