Myxoid fibroadenomas differ from conventional fibroadenomas: a hypothesis-generating study.
AIMS
Breast myxoid fibroadenomas (MFAs) are characterized by a distinctive hypocellular myxoid stroma, and occur sporadically or in the context of Carney complex, an inheritable condition caused by PRKAR1A-inactivating germline mutations. Conventional fibroadenomas (FAs) are underpinned by recurrent MED12 mutations in the stromal components of the lesions. The aim of this study was to investigate the genomic landscape of MFAs and compare it with that of conventional FAs.


METHODS AND RESULTS
Eleven MFAs 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 PRKAR1A mutations and non-synonymous mutations in six MFAs. Interestingly, in three of the MFAs 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 PRKAR1A 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 PRKAR1A somatic mutation was restricted to the stromal component.


CONCLUSION
MFAs lack MED12 mutations, and their stromal components seem not to harbour mutations in the 410 cancer genes tested. Whole-exome and/or whole-genome analyses of MFAs are required to elucidate their genetic drivers.
['Lozada|John R|JR|', 'Burke|Kathleen A|KA|', 'Maguire|Aoife|A|http://orcid.org/0000-0002-9120-6383', 'Pareja|Fresia|F|', 'Lim|Raymond S|RS|', 'Kim|Jisun|J|', 'Gularte-Merida|Rodrigo|R|http://orcid.org/0000-0002-4383-2523', 'Murray|Melissa P|MP|http://orcid.org/0000-0002-2935-6014', 'Brogi|Edi|E|', 'Weigelt|Britta|B|', 'Reis-Filho|Jorge S|JS|http://orcid.org/0000-0003-2969-3173', 'Geyer|Felipe C|FC|http://orcid.org/0000-0002-9625-2346']
D000328:Adult D001940:Breast D001943:Breast Neoplasms D015331:Cohort Studies D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit D005260:Female D018226:Fibroadenoma D059014:High-Throughput Nucleotide Sequencing D006801:Humans D056892:Mediator Complex D042282:Microdissection D008875:Middle Aged D009154:Mutation D017422:Sequence Analysis, DNA
fibroadenoma MED12 MSK-IMPACT PRKAR1A breast myxoma