Soft Tissue Tumors (including

The Human Soft Tissue Tumors (including GIST) qBiomarker Somatic Mutation PCR Array is a translational research tool that allows rapid, accurate, and comprehensive profiling of the top somatic mutations in human soft tissue tumor samples in the following genes: APC, BRAF, CTNNB1/beta-catenin, HRAS, KIT, KRAS, NF2, NRAS, PDGFRA, SMARCB1, and p53. These mutations warrant extensive investigation to enhance the understanding of carcinogenesis and identify potential drug targets. Numerous research studies have demonstrated the utility of individual and multiple somatic mutation status information in identifying key signaling transduction disruptions. For example, the mutation status of the EGFR and KRAS genes can predict the physiological response to certain drugs targeting these molecules. The Human Soft Tissue Tumor qBiomarker Somatic Mutation PCR Array, with its comprehensive content coverage, is designed for the study of mutations in the context of soft tissue tumors (including GIST) and has the potential for discovery and verification of drug target biomarkers for this cancer type and other cancer types in which these mutations have been identified. This array includes 83 DNA sequence mutation assays designed to detect the most frequent, functionally verified, and biologically significant mutations in human soft tissue tumors. These mutations were chosen from curated, comprehensive somatic mutation databases and peer-reviewed scientific literature, and represent the most frequently recurring somatic mutations compiled from over 4800 soft tissue tumor samples (including 3100 GIST samples). The simplicity of the product format and operating procedure allows routine somatic mutation profiling in any research laboratory with access to real-time PCR instruments.

APC: 3 Assays
The most commonly detected APC inactivation mutations are mainly composed of truncation mutations (due to nonsense mutations and frameshift mutations) and point mutations between codons 1250 and 1578.

BRAF: 1 Assay
The most important BRAF mutation in soft tissue tumors leads to increased kinase activity, the p. V600E mutation.

CTNNB1: 7 Assays
The most frequently detected CTNNB1/beta-catenin mutations result in abnormal signaling in the WNT signaling pathway. The mutated codons are mainly several serine/threonine residues targeted for phosphorylation by GSK-3beta.

HRAS: 5 Assays
The mutation assays include the most important HRAS mutations identified in cancers at codons 12, 13, and 61.

KIT: 27 Assays
The most frequently identified KIT gain-of-function mutations include the D816V point mutation, the exon 11 (juxtamembrane domain) deletion and point mutations, an exon 9 insertion mutation, and exon 13 point mutations.

KRAS: 6 Assays
The mutation assays include the most frequently occurring mutations in KRAS codons 12, 13, and 61. Mutations at these positions result in reduced intrinsic GTPase activity and/or cause KRAS to become unresponsive to RasGAP.

NF2: 6 Assays
NF2 is similar to some members of the ERM (ezrin, radixin, moesin) family of proteins and links cell-surface proteins with cytoskeletal components and proteins involved in cytoskeletal dynamics. Mutations in this gene are associated with neurofibromatosis type II which is characterized by nervous system and skin tumors and ocular abnormalities.

NRAS: 3 Assays
The mutation assays include the most important NRAS mutations at codons 12, 13, and 61.

PDGFRA: 15 Assays
The most frequently identified PDGFRA gain-of-function mutations include deletion, point mutation, and deletion-insertion mutations in regions p.D842-S847 and p.R554-E571 as well as the point mutations p.N659Y and p.T674I.

SMARCB1: 5 Assays
SMARCB1, as part of a complex, relieves repressive chromatin structures, allowing the transcriptional machinery to more effectively access its targets. Mutations in this tumor suppressor gene have been associated with malignant rhabdoid tumors.

TP53: 5 Assays
The most frequently detected somatic mutations in TP53 are largely composed of DNA-binding domain mutations which disrupt either DNA binding or protein structure.