Genomic profile of breast sarcomas: a comparison with malignant phyllodes tumours

• Published in: Breast cancer research and treatment 2019-04, Vol.174 (2), p.365-373
• Main Authors: Lim, Sue Zann, Ng, Cedric Chuan Young, Rajasegaran, Vikneswari, Guan, Peiyong, Selvarajan, Sathiyamoorthy, Thike, Aye Aye, Nasir, Nur Diyana Binte Md, Koh, Valerie Cui Yun, Tan, Benita Kiat Tee, Ong, Kong Wee, Teh, Bin Tean, Tan, Puay Hoon
• Format: Article
• Language: English
• Subjects: Aged; Analysis; Angiosarcoma; Breast cancer; Breast Neoplasms - genetics; Cancer genetics; Cancer research; Copy number; Deoxyribonucleic acid; DNA; DNA-Binding Proteins - genetics; Epidermal growth factor receptors; Female; Filamins - genetics; Formaldehyde; Gene mutation; Genes; Genetic aspects; Genetic Association Studies; Hemangiosarcoma - genetics; High-Throughput Nucleotide Sequencing - methods; Humans; Mediator Complex - genetics; Medicine; Medicine & Public Health; Middle Aged; Mutation; Neoplasm Proteins - genetics; Neurofibromin 1 - genetics; Oncology; Paraffin; Phyllodes Tumor - genetics; Preclinical Study; Proto-Oncogene Proteins - genetics; Quality control; Quality management; Repressor Proteins - genetics; Sarcoma; Sarcoma - genetics; Sequence Analysis, DNA - methods; Telomerase - genetics; Tumors
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-018-5067-5

Purpose We aimed to investigate the genomic profile of breast sarcomas (BS) and compare with that of malignant phyllodes tumours (MPT). Methods DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) specimens from 17 cases of BS diagnosed at Singapore General Hospital from January 1991 to December 2014. Targeted deep sequencing and copy number variation (CNV) analysis on 16 genes, which included recurrently mutated genes in phyllodes tumours and genes associated with breast cancer, were performed on these samples. Genetic alterations (GA) observed were summarised and analysed. Results Nine cases met the quality control requirements for both targeted deep sequencing and CNV analysis. Three (33.33%) were angiosarcomas and 6 (66.67%) were non-angiosarcomas. In the non-angiosarcoma group, 83.33% ( n  = 5) of the patients had GA in the TERT gene. The other commonly mutated genes in this group of tumours were MED 12 ( n  = 4, 66.67%), BCOR ( n  = 4, 66.67%), KMT2D ( n  = 3, 50%), FLNA ( n  = 3, 50%) and NF1 ( n  = 3, 50%). In contrast, none of the angiosarcomas had mutations or copy number alterations in TERT , MED 12 , BCOR , FLNA or NF1 . Eighty percent of patients with GA in TERT ( n  = 5) had concurrent mutations in MED 12 . Sixty percent ( n  = 3) of these cases also demonstrated GA in NF1 , PIK3CA or EGFR which are known cancer driver genes. Conclusions The non-angiosarcoma group of BS was found to share similar GA as those described for MPT, which may suggest a common origin and support their consideration as a similar group of tumours with regard to management and prognostication.