Distribution of MED12 mutations in fibroadenomas and phyllodes tumors of the breast—implications for tumor biology and pathological diagnosis. Issue 7 (30th April 2015)

• Record Type: Journal Article
• Authors: Pfarr, Nicole; Kriegsmann, Mark; Sinn, Peter; Klauschen, Frederick; Endris, Volker; Herpel, Esther; Muckenhuber, Alexander; Jesinghaus, Moritz; Klosterhalfen, Bernd; Penzel, Roland; Lennerz, Jochen K.; Weichert, Wilko; Stenzinger, Albrecht
• Is Part Of: Genes, chromosomes & cancer. Volume 54:Issue 7(2015:Jul.)
• Page Start: 444
• Page End: 452
• Publication Date: 2015-04-30
• Subjects: Cancer -- Genetic aspects -- Periodicals; 616.994042
• DOI: 10.1002/gcc.22256
• Languages: English
• ISSNs: 1045-2257

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Somatic mutations in exon 2 of <italic>MED12</italic> have been described in benign and malignant smooth muscle cell tumors suggesting a functional role in these neoplasms. Recently fibroadenomas of the breast were also reported to harbor <italic>MED12</italic> mutations. Hence, we explored <italic>MED12</italic> mutations in fibroepithelial tumors of the breast, histological subtypes of fibroadenomas and phyllodes tumors, to validate and extend previous efforts. Using conventional Sanger sequencing, we profiled 39 cases of fibroepithelial breast tumors comprising classic histological subtypes of fibroadenomas as well as benign and malignant phyllodes tumors for mutations in exon 2 of <italic>MED12</italic>. <italic>MED12</italic> mutations were detected in 60% of all tumor samples with the majority being missense mutations affecting codon 44. Additionally, we report novel in‐frame deletions that have not been described previously. Sixty‐two percent of the fibroadenomas harbored mutated <italic>MED12</italic> with intracanalicular fibroadenomas being the most frequently mutated histological subtype (82%). Of note, 8/11 of benign phyllodes tumors had <italic>MED12</italic> mutations while only 1/5 of malignant phyllodes tumors showed mutations in exon 2 of <italic>MED12</italic>. In conclusion, we confirm the frequent occurrence of <italic>MED12</italic> mutations in fibroadenomas, provide evidence that most intracanalicular fibroadenomas closely resembling benign phyllodes as well as benign phyllodes tumors harbor <italic>MED12</italic> mutations, and conclude that <italic>MED12</italic> mutations in malignant phyllodes tumors appear to be relatively rare. © 2015 Wiley Periodicals, Inc.</p> </abstract>