Identification of De Novo Germline Mutations in the HRPT2 Gene in Two Apparently Sporadic Cases with Challenging Parathyroid Tumor Diagnoses

• Type: Article in International Scientific Journal
• Date: 2011

Authors

Branca Maria Cavaco (Author) Other; Rita Santos (Author) Other; Ana Felix (Author) Other; Davide Carvalho (Author) FMUP; Jose Manuel Lopes (Author) FMUP; Rita Domingues (Author) Other; Marta Sirgado (Author) Other; Nadia Rei (Author) Other; Fernando Fonseca (Author) Other; Jorge Rosa Santos (Author) Other; Luis Sobrinho (Author) Other; Valeriano Leite (Author) Other

Journal

Title: Endocrine Pathology

Vol. 22

Pages: 44-52

ISSN: 1046-3976

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 18 Citations

Scopus - 23 Citations

Scientific classification

FOS: Medical and Health sciences > Clinical medicine

Other information

Authenticus ID: P-002-TN0

DOI: 10.1007/s12022-011-9151-1

Abstract (EN): The diagnosis of parathyroid carcinomas is often difficult. HRPT2 mutations have been identified in familial [hyperparathyroidism-jaw tumor (HPT-JT) syndrome] and sporadic parathyroid carcinomas, supporting that HRPT2 mutations may confer a malignant potential to parathyroid tumors. In this study, we report the clinical, histopathological, and genetic investigation of two unrelated cases, whom had apparently sporadic malignant parathyroid tumors, initially diagnosed as adenomas. In one case, the differential diagnosis was complicated by cervical seeding of parathyroid tumor cells. Genetic studies identified de novo HRPT2 germline mutations in cases 1 (c.518_521delTGTC [p.Ser174LysfsX27]) and 2 (c.226 C > T [p.Arg76X]), unveiling the hereditary HPT-JT syndrome in both patients. Furthermore, the identification of somatic mutations in the patientsaEuroY parathyroid tumors provided evidence for complete inactivation of the HRPT2 gene, which was consistent with the tumor malignant features. The sensitivity of parafibromin immunostaining to detect HRPT2 mutations was limited. The present data suggests that patients with apparently sporadic parathyroid carcinomas, or parathyroid tumors with atypical histological features, should undergo molecular genetic testing, as it may detect germline HRPT2 mutations. Establishing the diagnosis of hereditary HPT-JT syndrome is relevant for clinical counseling and management of the carriers and their relatives.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9