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Identification of MEN1 and HRPT2 somatic mutations in paraffin-embedded (sporadic) parathyroid carcinomas.
Clin Endocrinol (Oxf). 2007 Sep; 67(3):370-6.CE

Abstract

OBJECTIVE

Parathyroid carcinoma remains difficult to diagnose. Recently, it has been shown that mutations in the HRPT2 gene (encoding parafibromin) are associated with the development of parathyroid carcinoma. Although MEN1 is not typically thought to be involved in carcinoma formation, parathyroid carcinoma may be an extremely rare feature of the multiple endocrine neoplasia type 1 (MEN1) syndrome. We recently concluded that loss of heterozygosity (LOH) of the MEN1 gene is present in a relatively large number of parathyroid carcinomas, often in combination with LOH at the HRPT2 locus. The aim of this study was to evaluate the role of MEN1 and HRPT2 mutations in sporadic parathyroid tumours fulfilling histological criteria for malignancy.

PATIENTS AND DESIGN

Formalin-fixed, paraffin-embedded (FFPE) parathyroid carcinoma tissue from 28 cases identified in the period 1985-2000 in the Netherlands was studied. HRPT2 (27/28 cases) and MEN1 (23/28 cases) were analysed by direct sequencing.

RESULTS

Somatic MEN1 mutations were found in three of 23 (13%) sporadic parathyroid carcinoma cases; these consisted of one missense and two frameshift mutations. One of the latter two cases displayed lymph-node and lung metastases during follow-up. Six HRPT2 mutations were found in 4/27 cases (15%): five were truncating mutations and one was a missense mutation. Consistent with previously published reports, we found double mutations (2x) and germline mutations (2x) in apparently sporadic parathyroid carcinomas.

CONCLUSIONS

These results suggest that not only HRPT2 but also MEN1 mutations may play a role in sporadic parathyroid cancer formation.

Authors+Show Affiliations

Department of Pathology, Leiden University Medical Centre, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17555500

Citation

Haven, C J., et al. "Identification of MEN1 and HRPT2 Somatic Mutations in Paraffin-embedded (sporadic) Parathyroid Carcinomas." Clinical Endocrinology, vol. 67, no. 3, 2007, pp. 370-6.
Haven CJ, van Puijenbroek M, Tan MH, et al. Identification of MEN1 and HRPT2 somatic mutations in paraffin-embedded (sporadic) parathyroid carcinomas. Clin Endocrinol (Oxf). 2007;67(3):370-6.
Haven, C. J., van Puijenbroek, M., Tan, M. H., Teh, B. T., Fleuren, G. J., van Wezel, T., & Morreau, H. (2007). Identification of MEN1 and HRPT2 somatic mutations in paraffin-embedded (sporadic) parathyroid carcinomas. Clinical Endocrinology, 67(3), 370-6.
Haven CJ, et al. Identification of MEN1 and HRPT2 Somatic Mutations in Paraffin-embedded (sporadic) Parathyroid Carcinomas. Clin Endocrinol (Oxf). 2007;67(3):370-6. PubMed PMID: 17555500.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification of MEN1 and HRPT2 somatic mutations in paraffin-embedded (sporadic) parathyroid carcinomas. AU - Haven,C J, AU - van Puijenbroek,M, AU - Tan,M H, AU - Teh,B T, AU - Fleuren,G J, AU - van Wezel,T, AU - Morreau,H, Y1 - 2007/06/06/ PY - 2007/6/9/pubmed PY - 2011/10/28/medline PY - 2007/6/9/entrez SP - 370 EP - 6 JF - Clinical endocrinology JO - Clin Endocrinol (Oxf) VL - 67 IS - 3 N2 - OBJECTIVE: Parathyroid carcinoma remains difficult to diagnose. Recently, it has been shown that mutations in the HRPT2 gene (encoding parafibromin) are associated with the development of parathyroid carcinoma. Although MEN1 is not typically thought to be involved in carcinoma formation, parathyroid carcinoma may be an extremely rare feature of the multiple endocrine neoplasia type 1 (MEN1) syndrome. We recently concluded that loss of heterozygosity (LOH) of the MEN1 gene is present in a relatively large number of parathyroid carcinomas, often in combination with LOH at the HRPT2 locus. The aim of this study was to evaluate the role of MEN1 and HRPT2 mutations in sporadic parathyroid tumours fulfilling histological criteria for malignancy. PATIENTS AND DESIGN: Formalin-fixed, paraffin-embedded (FFPE) parathyroid carcinoma tissue from 28 cases identified in the period 1985-2000 in the Netherlands was studied. HRPT2 (27/28 cases) and MEN1 (23/28 cases) were analysed by direct sequencing. RESULTS: Somatic MEN1 mutations were found in three of 23 (13%) sporadic parathyroid carcinoma cases; these consisted of one missense and two frameshift mutations. One of the latter two cases displayed lymph-node and lung metastases during follow-up. Six HRPT2 mutations were found in 4/27 cases (15%): five were truncating mutations and one was a missense mutation. Consistent with previously published reports, we found double mutations (2x) and germline mutations (2x) in apparently sporadic parathyroid carcinomas. CONCLUSIONS: These results suggest that not only HRPT2 but also MEN1 mutations may play a role in sporadic parathyroid cancer formation. SN - 0300-0664 UR - https://www.unboundmedicine.com/medline/citation/17555500/Identification_of_MEN1_and_HRPT2_somatic_mutations_in_paraffin_embedded__sporadic__parathyroid_carcinomas_ L2 - https://doi.org/10.1111/j.1365-2265.2007.02894.x DB - PRIME DP - Unbound Medicine ER -