GNAS mutations in fibrous dysplasia: A comparative study of standard sequencing and locked nucleic acid PCR sequencing on decalcified and nondecalcified formalin-fixed paraffin-embedded tissues Journal Article
| Authors: | Jour, G.; Oultache, A.; Sadowska, J.; Mitchell, T.; Healey, J.; Nafa, K.; Hameed, M. |
| Article Title: | GNAS mutations in fibrous dysplasia: A comparative study of standard sequencing and locked nucleic acid PCR sequencing on decalcified and nondecalcified formalin-fixed paraffin-embedded tissues |
| Abstract: | It is well known that fibrous dysplasia (FD) is characterized by the presence of activating mutations involving G-nucleotide binding protein-α subunit (GNAS) involving codon R201 and rarely codon 227 with a mutation frequency between 45% and 93%. Herein, we investigate the sensitivity of detection of GNAS mutations in exons 8 and 9 using a standard and a highly sensitive locked nucleic acid polymerase chain reaction (LNA-PCR) sequencing in 52 cases of FD. In view of the recent report of GNAS mutations in a small number of low-grade osteosarcomas, we also tested in addition 12 cases of low-grade osteosarcomas. GNAS exon 8 mutations p.R201H (31%), p.R201C (15%), and p.R201S (2%) were identified in 50% of FD cases. LNA-PCR sequencing identified only 1 positive case within the mutation negative cases tested by standard PCR and Sanger sequencing. No mutations were identified in any of the low-grade osteosarcomas by standard and LNA-PCR sequencing. There was no association between age, site, size, specimen type, and mutational status. No exon 9 or codon 227 mutations were identified in any of tested cases. There was a significant difference in the sensitivity of the assay between decalcified and nondecalcified FDs (31% vs. 70%, P=0.002). LNA-PCR has no added value in enhancing detection sensitivity for GNAS mutations in FD. In addition to decalcification, innate somatic mosaicism contributes to the decreased sensitivity in mutation detection. © 2015 Wolters Kluwer Health, Inc. |
| Keywords: | fibrous dysplasia; sanger sequencing; gnas- α mutations; locked nucleic acid pcr sequencing (lna-pcr sequencing) |
| Journal Title: | Applied Immunohistochemistry & Molecular Morphology |
| Volume: | 24 |
| Issue: | 9 |
| ISSN: | 1541-2016 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2016-10-01 |
| Start Page: | 660 |
| End Page: | 667 |
| Language: | English |
| DOI: | 10.1097/pai.0000000000000242 |
| PROVIDER: | scopus |
| PUBMED: | 26574629 |
| PMCID: | PMC5563825 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 6 December 2016 -- Source: Scopus |
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