Frequent MED12 mutations in phyllodes tumours of the breast

• Published in: British journal of cancer Vol. 112; no. 10; pp. 1703 - 1708
• Main Authors: Yoshida, M, Sekine, S, Ogawa, R, Yoshida, H, Maeshima, A, Kanai, Y, Kinoshita, T, Ochiai, A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.05.2015; Nature Publishing Group
• Subjects: 692/4028/67/1347; 692/4028/67/68; Adolescent; Adult; Aged; Biomedical and Life Sciences; Biomedicine; Breast Neoplasms - genetics; Cancer Research; Drug Resistance; Epidemiology; Female; Fibroadenoma - genetics; full-paper; Humans; Mediator Complex - genetics; Middle Aged; Molecular Medicine; Mutation - genetics; Oncology; Phyllodes Tumor - genetics; Young Adult; fibroadenoma; breast; phyllodes tumour
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2015.116

Background: Phyllodes tumours are rare fibroepithelial tumours of the breast, that include benign, borderline, and malignant lesions. Although the molecular basis of phyllodes tumours largely remains unknown, a recent exome study identified MED12 mutations as a sole recurrent genetic alteration in fibroadenoma, a common benign fibroepithelial tumour that shares some histological features with the phyllodes tumour. Methods: Forty-six phyllodes tumours and 58 fibroadenomas of the breast were analysed for MED12 mutations by using Sanger sequencing. Results: MED12 mutations were identified in 37 out of the 46 phyllodes tumours (80%). The prevalence of MED12 mutations was similar among benign (15/18, 83%), borderline (12/15, 80%), and malignant tumours (10/13, 77%). MED12 mutations were also identified in 36 of the 58 fibroadenomas (62%). The mutations were frequent among intracanalicular-type (24/32, 75%) and complex-type lesions (4/6, 67%), but were significantly less common among the pericanalicular-type lesions (8/20, 40%). A microdissection-based analysis showed that MED12 mutations were confined to the stromal components in both phyllodes tumours and fibroadenomas. Conclusions: MED12 mutations were frequent among the phyllodes tumours of the breast, regardless of the tumour grade. Phyllodes tumours and fibroadenomas share, at least in part, a common genetic background.