PMID- 17555500
OWN - NLM
STAT- MEDLINE
DCOM- 20111027
LR  - 20220331
IS  - 0300-0664 (Print)
IS  - 0300-0664 (Linking)
VI  - 67
IP  - 3
DP  - 2007 Sep
TI  - Identification of MEN1 and HRPT2 somatic mutations in paraffin-embedded 
      (sporadic) parathyroid carcinomas.
PG  - 370-6
AB  - 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.
FAU - Haven, C J
AU  - Haven CJ
AD  - Department of Pathology, Leiden University Medical Centre, The Netherlands.
FAU - van Puijenbroek, M
AU  - van Puijenbroek M
FAU - Tan, M H
AU  - Tan MH
FAU - Teh, B T
AU  - Teh BT
FAU - Fleuren, G J
AU  - Fleuren GJ
FAU - van Wezel, T
AU  - van Wezel T
FAU - Morreau, H
AU  - Morreau H
LA  - eng
PT  - Journal Article
DEP - 20070606
PL  - England
TA  - Clin Endocrinol (Oxf)
JT  - Clinical endocrinology
JID - 0346653
RN  - 0 (CDC73 protein, human)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Tumor Suppressor Proteins)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biological Specimen Banks
MH  - Cohort Studies
MH  - DNA Mutational Analysis
MH  - Female
MH  - Frameshift Mutation
MH  - Humans
MH  - Loss of Heterozygosity/genetics
MH  - Male
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/*genetics/pathology
MH  - Mutation, Missense
MH  - Netherlands
MH  - Paraffin Embedding
MH  - Parathyroid Neoplasms/*genetics/pathology
MH  - Proto-Oncogene Proteins/*genetics
MH  - Tumor Suppressor Proteins/*genetics
EDAT- 2007/06/09 09:00
MHDA- 2011/10/28 06:00
CRDT- 2007/06/09 09:00
PHST- 2007/06/09 09:00 [pubmed]
PHST- 2011/10/28 06:00 [medline]
PHST- 2007/06/09 09:00 [entrez]
AID - CEN2894 [pii]
AID - 10.1111/j.1365-2265.2007.02894.x [doi]
PST - ppublish
SO  - Clin Endocrinol (Oxf). 2007 Sep;67(3):370-6. doi: 
      10.1111/j.1365-2265.2007.02894.x. Epub 2007 Jun 6.