GNAS1 mutations occur more commonly than previously thought in intramuscular myxoma.

Abstract

Mutation detection plays an important role in diagnostic pathology, not only in providing a tissue diagnosis, but also in predicting response to antitumourigenic agents. However, mutation detection strategies are often hampered by masking of mutant alleles by wild-type sequences. Coamplification at lower denaturation temperature PCR (COLD-PCR) reportedly increases the proportion of rare variant sequences in a wild-type background by using PCR cycles in which the denaturation temperature is reduced to favour product formation with lower melt temperatures and heteroduplexes arising from minor variants. Intramuscular myxoma is a rare benign soft tissue neoplasm that occurs sporadically and less commonly in association with fibrous dysplasia (Mazabraud's syndrome). Fibrous dysplasia results from activating GNAS1 mutations, and the same mutations have been identified in small numbers of intramuscular myxoma. The aim of the study was primarily to establish whether COLD-PCR is more sensitive than conventional PCR; this was achieved by testing for GNAS1 mutations in intramuscular myxomas using the two methodologies. Mutations were detected in 8 of 28 (29%) cases of intramuscular myxomas using conventional PCR followed by mutation-specific restriction enzyme digestion (PCR-MSRED) whereas 17 of 28 (61%) mutations were detected using COLD-PCR/MSRED. Mutations were detected in two cases where a diagnosis of low-grade myxofibrosarcoma had been favoured over intramuscular myxoma. No mutations were detected in an additional 9 low-grade and 19 high-grade myxofibrosarcomas, and another 40 control samples. This study shows the power of COLD-PCR compared with conventional PCR in mutation detection, and shows that GNAS1 mutation detection increases diagnostic accuracy when distinguishing between intramuscular myxoma and low-grade myxofibrosarcoma.

• Authors: David Delaney, Tim C Diss, Nadege Presneau, Sandra Hing, Fitim Berisha, Bernadine D Idowu, P O'Donnell, John A Skinner, Roberto Tirabosco, Adrienne M Flanagan
• Journal: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc (Mod Pathol) Vol. 22 Issue 5 Pg. 718-24 (May 2009) ISSN: 1530-0285 [Electronic] United States
• PMID: 19287459 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chromogranins
• GNAS protein, human
• GTP-Binding Protein alpha Subunits, Gs

Topics

• Chromogranins
• Cold Temperature
• DNA Mutational Analysis
• Diagnosis, Differential
• Fibrosarcoma (genetics, pathology)
• GTP-Binding Protein alpha Subunits, Gs (genetics)
• Humans
• Mutation
• Myxoma (genetics, pathology)
• Polymerase Chain Reaction (methods)
• Sensitivity and Specificity
• Soft Tissue Neoplasms (genetics, pathology)