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Myxoid fibroadenomas differ from conventional fibroadenomas: a hypothesis‐generating study
Author(s) -
Lozada John R,
Burke Kathleen A,
Maguire Aoife,
Pareja Fresia,
Lim Raymond S,
Kim Jisun,
GularteMerida Rodrigo,
Murray Melissa P,
Brogi Edi,
Weigelt Britta,
ReisFilho Jorge S,
Geyer Felipe C
Publication year - 2017
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13258
Subject(s) - germline mutation , germline , context (archaeology) , carney complex , stromal cell , biology , sanger sequencing , breast cancer , mutation , pathology , genetic heterogeneity , fibroadenoma , cancer research , genetics , cancer , medicine , gene , phenotype , paleontology
Aims Breast myxoid fibroadenomas ( MFA s) are characterized by a distinctive hypocellular myxoid stroma, and occur sporadically or in the context of Carney complex, an inheritable condition caused by PRKAR 1A ‐inactivating germline mutations. Conventional fibroadenomas ( FA s) are underpinned by recurrent MED 12 mutations in the stromal components of the lesions. The aim of this study was to investigate the genomic landscape of MFA s and compare it with that of conventional FA s. Methods and results Eleven MFA s from patients without clinical and/or genetic evidence of Carney complex were retrieved. DNA samples of tumour and matching normal tissue were subjected to massively parallel sequencing using the Memorial Sloan Kettering‐Integrated Mutation Profiling of Actionable Cancer Targets ( MSK ‐ IMPACT ) assay, an assay targeting 410 cancer genes. Genetic alterations detected by MSK ‐ IMPACT were tested in samples in which the stromal and epithelial components were separately laser capture‐microdissected. Sequencing revealed no germline PRKAR 1A mutations and non‐synonymous mutations in six MFA s. Interestingly, in three of the MFA s in which the stromal and epithelial components were separately microdissected, the mutations were found to be restricted to the epithelial rather than the stromal component. The sole exception was a lesion harbouring a somatic truncating PRKAR 1A mutation. Upon histological re‐review, this case was reclassified as a breast myxoma, consistent with the spectrum of tumous observed in Carney complex patients. In this case, the PRKAR 1A somatic mutation was restricted to the stromal component. Conclusion MFA s lack MED 12 mutations, and their stromal components seem not to harbour mutations in the 410 cancer genes tested. Whole‐exome and/or whole‐genome analyses of MFA s are required to elucidate their genetic drivers.