Mutational profiling of brain metastasis from breast cancer: matched pair analysis of targeted sequencing between brain metastasis and primary breast cancer
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Ji Yun Lee1,*, Kyunghee Park2,*, Sung Hee Lim1, Hae Su Kim1, Kwai Han Yoo1, Ki Sun Jung1, Haa-Na Song1, Mineui Hong3, In-Gu Do3, TaeJin Ahn2, Se Kyung Lee4, Soo Youn Bae4, Seok Won Kim4, Jeong Eon Lee4, Seok Jin Nam4, Duk-Hwan Kim5, Hae Hyun Jung6, Ji-Yeon Kim1, Jin Seok Ahn1, Young-Hyuck Im1, Yeon Hee Park1
1Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
2Samsung Genomic Institute, Samsung Biological Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
3Center of Companion Diagnostics, Innovative Cancer Medicine Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
4Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
5Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Korea
6Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
*These authors have contributed equally to this work
Yeon Hee Park, e-mail: [email protected]
Keywords: breast cancer, brain metastasis, gene, mutation, mechanism
Received: August 27, 2015 Accepted: October 06, 2015 Published: October 20, 2015
Although breast cancer is the second most common cause of brain metastasis with a notable increase of incidence, genes that mediate breast cancer brain metastasis (BCBM) are not fully understood. To study the molecular nature of brain metastasis, we performed gene expression profiling of brain metastasis and matched primary breast cancer (BC). We used the Ion AmpliSeq Cancer Panel v2 covering 2,855 mutations from 50 cancer genes to analyze 18 primary BC and 42 BCBM including 15 matched pairs. The most common BCBM subtypes were triple-negative (42.9%) and basal-like (36.6%). In a total of 42 BCBM samples, 32 (76.2%) harbored at least one mutation (median 1, range 0–7 mutations). Frequently detected somatic mutations included TP53 (59.5%), MLH1 (14.3%), PIK3CA (14.3%), and KIT (7.1%). We compared BCBM with patient-matched primary BC specimens. There were no significant differences in mutation profiles between the two groups. Notably, gene expression in BCBM such as TP53, PIK3CA, KIT, MLH1, and RB1 also seemed to be present in primary breast cancers. The TP53 mutation frequency was higher in BCBM than in primary BC (59.5% vs 38.9%, respectively). In conclusion, we found actionable gene alterations in BCBM that were maintained in primary BC. Further studies with functional testing and a delineation of the role of these genes in specific steps of the metastatic process should lead to a better understanding of the biology of metastasis and its susceptibility to treatment.
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