Germline BRCA1 Mutation Detected in a Multiple Endocrine Neoplasia Type 2 Case With RET Codon 634 Mutation

Frontiers in Genetics

Kornélia Baghy¹  Zoltán Sápi¹  Balázs Sarkadi²  Attila Patócs³  Gábor Nyirő⁴  István Likó⁶ 

[1] 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary;2nd Department of Medicine, Semmelweis University, Budapest, Hungary;Department of Laboratory Medicine, Semmelweis University, Budapest, Hungary;HAS-SE Molecular Medicine Research Group, Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary;HAS-SE “Lendulet” Hereditary Endocrine Tumors Research Group, Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary;National Bionics Program, Budapest, Hungary;

关键词: medullary thyroid cancer;    RET mutation;    BRCA1 mutation;    multiple endocrine neoplasia type 2;    cancer genetics;   

DOI  :  10.3389/fgene.2019.00544

来源: DOAJ

【 摘 要 】

Coincidences of more than one pathogenic mutation in high and/or moderate risk-associated cancer genes have been rarely reported, and the implication for disease progression has been debated. We present a case harboring two autosomal dominant inherited mutations potentially aggravating the phenotype.Case report: A 16-year-old female was referred to the Endocrine Unit due to two palpable thyroid nodules and hair loss. Two hypoechoic, inhomogeneous masses with microcalcification in the thyroid gland were confirmed as medullary thyroid carcinoma. Genetic testing revealed a pathogenic heterozygous RET mutation associated with multiple endocrine neoplasia type 2 (MEN2). Furthermore, genetic screening identified the same mutation in the proband’s clinically negative brother as well as in his two sons. The proband’s mother and maternal aunt died of breast cancer. No samples were available from the deceased. The proband underwent further genetic counseling and BRCA1/2 testing. A novel, frameshift heterozygous BRCA1 mutation (BRCA1 p.Ile90Serfs, NC_000017.10:g.41256905_41256917) was identified in the proband, but it was absent in the brother and father, indicative of maternal inheritance. Breast or ovarian cancer was neither detected in our case at initial presentation nor during the 6-year follow-up.Conclusion: Coincidence of two monogenic autosomal dominant tumor syndromes is extremely rare, but it represents a significant therapeutic and cancer surveillance challenge. Due to the wider use of next generation sequencing in clinical practice, similar situations may occur more frequently.

【 授权许可】

Unknown