Carney complex with PRKAR1A variant and breast/fibrolamellar carcinomas

Area of Science:

• Genetics
• Oncology
• Endocrinology

Background:

• Carney complex is a rare genetic disorder linked to PRKAR1A gene mutations.
• It classically presents with myxomas, lentigines, and endocrine tumors.
• The full spectrum of tumors associated with PRKAR1A loss of function is not fully understood.

Purpose of the Study:

• To report a case of Carney complex with an unusual tumor presentation.
• To expand the understanding of the phenotypic variability in Carney complex.
• To investigate the role of PRKAR1A loss in oncogenesis beyond classical tissues.

Main Methods:

• Molecular confirmation of Carney complex diagnosis.
• Identification of a de novo PRKAR1A splice-site variant (NM_002734.5):c.348+1G>A.
• Clinical documentation of patient's tumor types: invasive breast carcinoma and fibrolamellar hepatocellular carcinoma.

Main Results:

• The patient presented with Carney complex and two rare malignancies: young-onset invasive breast carcinoma and fibrolamellar hepatocellular carcinoma.
• The fibrolamellar hepatocellular carcinoma lacked the typical DNAJB1-PRKACA fusion.
• This case expands the known tumor spectrum associated with PRKAR1A variants.

Conclusions:

• PRKAR1A loss of function may contribute to oncogenesis in tissues beyond endocrine and mesenchymal types.
• This case highlights the importance of ongoing surveillance for individuals with Carney complex.
• The phenotypic variability of Carney complex is broader than previously recognized.