Kelly Kyker-Snowman1, Bracha Erlanger Avigdor1, Mansoor Nasim2, Ashley Cimino-Mathews1,3, Sarah J Wheelan4,5,6, Pedram Argani7,8,9, Ben Ho Park10,11,12. 1. Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 2. Department of Anatomic Pathology, Northwell Pathology, Northshore University Hospital Long Island Jewish Medical Center, Cohen Children Hospital, Lake Success, NY, 11040, USA. 3. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 4. Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. swheelan@jhmi.edu. 5. Department of Biostatistics, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. swheelan@jhmi.edu. 6. , 1550 Orleans St. CRB II, Room 1M51, Baltimore, MD, 21287, USA. swheelan@jhmi.edu. 7. Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. pargani@jhmi.edu. 8. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. pargani@jhmi.edu. 9. , Weinberg Building Room 2242, Baltimore, MD, 21231-2410, USA. pargani@jhmi.edu. 10. Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA. bpark2@jhmi.edu. 11. Department of Chemical and Biomolecular Engineering, The Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA. bpark2@jhmi.edu. 12. , 1650 Orleans Street, CRB1 Room 151, Baltimore, MD, 21287, USA. bpark2@jhmi.edu.
Abstract
BACKGROUND/ PURPOSE: Tumor heterogeneity is a now well-recognized phenomenon that can affect the classification, prognosis and treatment of human cancers. Heterogeneity is often described in primary breast cancers based upon histologic subtypes, hormone- and HER2-receptor status, and immunolabeling for various markers, which can be seen within a single tumor as mixed cellular populations, or as separate discrete foci. EXPERIMENTAL DESIGN/ METHODS: Here, we present a case report of a patient's primary breast cancer that had two separate but adjacent histologic components, one that was estrogen receptor (ER) positive, and the other ER negative. Each component was subjected to whole exome sequencing and compared for gene identity to determine clonal origin. RESULTS: Using prior bioinformatic tools, we demonstrated that both the ER positive and negative components shared many variants, including passenger and driver alterations. Copy number variations also supported the two components were derived from a single common clone. CONCLUSIONS: These analyses strongly suggest that the two ER components of this patient's breast cancer were derived from the same clonal origin. Our results have implications for the evolution of breast cancers with mixed histologies, and how they might be best managed for optimal therapy.
BACKGROUND/ PURPOSE:Tumor heterogeneity is a now well-recognized phenomenon that can affect the classification, prognosis and treatment of humancancers. Heterogeneity is often described in primary breast cancers based upon histologic subtypes, hormone- and HER2-receptor status, and immunolabeling for various markers, which can be seen within a single tumor as mixed cellular populations, or as separate discrete foci. EXPERIMENTAL DESIGN/ METHODS: Here, we present a case report of a patient's primary breast cancer that had two separate but adjacent histologic components, one that was estrogen receptor (ER) positive, and the other ER negative. Each component was subjected to whole exome sequencing and compared for gene identity to determine clonal origin. RESULTS: Using prior bioinformatic tools, we demonstrated that both the ER positive and negative components shared many variants, including passenger and driver alterations. Copy number variations also supported the two components were derived from a single common clone. CONCLUSIONS: These analyses strongly suggest that the two ER components of this patient's breast cancer were derived from the same clonal origin. Our results have implications for the evolution of breast cancers with mixed histologies, and how they might be best managed for optimal therapy.
Entities:
Keywords:
Breast cancer; Estrogen receptor; Whole exome sequencing
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