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

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Abstract

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 MED12 (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, MED12, BCOR, FLNA or NF1. Eighty percent of patients with GA in TERT (n = 5) had concurrent mutations in MED12. 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.

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Acknowledgements

This work was supported by funding from the Singapore General Hospital Research Grant 2016.

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Authors and Affiliations

  1. SingHealth Duke-National University of Singapore Breast Centre, Singapore, Singapore

    Sue Zann Lim, Benita Kiat Tee Tan & Kong Wee Ong

  2. Laboratory of Cancer Epigenome, National Cancer Centre Singapore, Singapore, Singapore

    Cedric Chuan Young Ng, Vikneswari Rajasegaran & Bin Tean Teh

  3. Division of Cancer and Stem Cell Biology, Duke-National University of Singapore Medical School, Singapore, Singapore

    Cedric Chuan Young Ng, Vikneswari Rajasegaran & Bin Tean Teh

  4. Integrated Biostatistics and Bioinformatics Programme, Duke-National University of Singapore Medical School, Singapore, Singapore

    Peiyong Guan

  5. Department of Anatomical Pathology, Singapore General Hospital, Singapore, Singapore

    Sathiyamoorthy Selvarajan, Aye Aye Thike, Nur Diyana Binte Md Nasir & Valerie Cui Yun Koh

  6. Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

    Bin Tean Teh

  7. Institute of Molecular and Cellular Biology, Singapore, Singapore

    Bin Tean Teh

  8. Division of Pathology, Singapore General Hospital, Level 7, Diagnostics Tower, Academia, 20 College Road, Singapore, 169856, Singapore

    Puay Hoon Tan

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  1. Sue Zann Lim
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Correspondence to Puay Hoon Tan.

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Lim, S.Z., Ng, C.C.Y., Rajasegaran, V. et al. Genomic profile of breast sarcomas: a comparison with malignant phyllodes tumours. Breast Cancer Res Treat 174, 365–373 (2019). https://doi.org/10.1007/s10549-018-5067-5

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