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Detection of somatic mutations by high-resolution DNA melting (HRM) analysis in multiple cancers
Journal article   Open access   Peer reviewed

Detection of somatic mutations by high-resolution DNA melting (HRM) analysis in multiple cancers

Jesus Gonzalez-Bosquet, Jacob Calcei, Jun S Wei, Montserrat Garcia-Closas, Mark E Sherman, Stephen Hewitt, Joseph Vockley, Jolanta Lissowska, Hannah P Yang, Javed Khan, …
PloS one, Vol.6(1), pp.e14522-e14522
01/17/2011
DOI: 10.1371/journal.pone.0014522
PMCID: PMC3022009
PMID: 21264207
url
https://doi.org/10.1371/journal.pone.0014522View
Published (Version of record) Open Access

Abstract

Identification of somatic mutations in cancer is a major goal for understanding and monitoring the events related to cancer initiation and progression. High resolution melting (HRM) curve analysis represents a fast, post-PCR high-throughput method for scanning somatic sequence alterations in target genes. The aim of this study was to assess the sensitivity and specificity of HRM analysis for tumor mutation screening in a range of tumor samples, which included 216 frozen pediatric small rounded blue-cell tumors as well as 180 paraffin-embedded tumors from breast, endometrial and ovarian cancers (60 of each). HRM analysis was performed in exons of the following candidate genes known to harbor established commonly observed mutations: PIK3CA, ERBB2, KRAS, TP53, EGFR, BRAF, GATA3, and FGFR3. Bi-directional sequencing analysis was used to determine the accuracy of the HRM analysis. For the 39 mutations observed in frozen samples, the sensitivity and specificity of HRM analysis were 97% and 87%, respectively. There were 67 mutation/variants in the paraffin-embedded samples, and the sensitivity and specificity for the HRM analysis were 88% and 80%, respectively. Paraffin-embedded samples require higher quantity of purified DNA for high performance. In summary, HRM analysis is a promising moderate-throughput screening test for mutations among known candidate genomic regions. Although the overall accuracy appears to be better in frozen specimens, somatic alterations were detected in DNA extracted from paraffin-embedded samples.
Mutation Paraffin Embedding Frozen Sections Neoplasms - genetics Biopsy Humans Nucleic Acid Denaturation - genetics DNA, Neoplasm - genetics DNA Mutational Analysis - methods Neoplasm Proteins - genetics

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