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. We sought to investigate the genomic landscape of
MFAs and compare it to 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 tumor and matching normal
tissue were subjected to massively parallel sequencing using MSK-IMPACT, an
assay targeting 410 cancer genes. Genetic alterations detected by MSK-IMPACT
were tested in samples where the stromal and epithelial components were
separately laser capture microdissected. Sequencing revealed no germline
PRKAR1A mutations and non-synonymous mutations detected
in six MFAs. Interestingly, in three of the MFAs where 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 harboring a somatic truncating
PRKAR1A mutation. Upon histologic re-review, this case
was reclassified as a breast myxoma, consistent with the spectrum of tumors
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
component seems not to harbor mutations in the 410 cancer genes tested.
Whole-exome and/or whole-genome analyses of MFAs are required to elucidate
their genetic drivers.