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CANCER SOMATIC MUTATION PROFILE (BONE MARROW)

Test Code: CSMPBM
Description: Section Director: James Zehnder, M.D.
Section Director: Iris Schrijver, M.D.

The acquisition of detailed genomic information in a variety of cancers has demonstrated that a core group of signaling pathways commonly acquire activating mutations. This has led to a paradigm shift in cancer therapy; from knowing the organ of origin and histology as the basis for therapy to also incorporating mutations which may be common to a variety of cancers into clinical decisions. For example activating mutations in BRAF are common in melanoma, lung cancer, thyroid cancer, colorectal cancer and hematologic malignancies. Knowledge of specific mutations may also guide therapeutic decision making to optimally utilize targeted therapies. For example, in non-small cell lung cancer (NSCLC) activating mutations in the epidermal growth factor receptor (EGFR) predict response to tyrosine kinase inhibitors gefitinib and erlotinib. On the other hand, activating mutations in KRAS, BRAF and PI3 kinase portend resistance to monoclonal antibodies targeting the extracellular EGFR domain (e.g., cetuximab).

The mutations detected with this assay are all potentially clinically actionable, typically involving signal pathway activating mutations which have targeted therapies available (some may require enrollment in clinical trials). The Cancer Somatic Mutation panel is a highly multiplexed targeted sequencing assay for detecting somatic mutations in 48 genes.

The next generation sequencing (NGS) portion of this assay begins with hybridization of optimized oligonucleotide probes upstream and downstream of the regions of interest. Each probe includes a target capture sequence and an adapter sequence used in subsequent amplification reaction. A proprietary extension-ligation reaction (Illumina) extends across the region of interest, followed by ligation to unite the two probes. This creates a new template strand and gives the assay excellent specificity. Extension-ligation templates are PCR amplified and two unique sample specific indices are incorporated. The final reaction product contains amplicons that are ready for sequencing. An integrated bead-based normalization procedure allows for volumetric library pooling. Pooled amplicon libraries are loaded directly onto the MiSeq system.

The SNaPshotTM methodology which uses a single base extension step with a labeled ddNTP is used to detect mutations in IDH2 and DNMT3A.

For additional information please contact our Customer Service at (877) 717-3733.

TO SEND A SPECIMEN FOR CONSULTATION

For information regarding clinical trials linked to specific cancer mutations: www.clinicaltrials.gov.

Regarding clinical trials at Stanford University Medical Center see Clinical Trials at Stanford.

A full list of targeted regions is available at http://stanfordlab.com/cancer_somatic_mutation_list.htm

Genes tested by Next Generation Sequencing:

AKT1 GNA11 NPM1
ALK GNAQ NRAS
APC GNAS PDGFRA
ATM HNF1A PIK3CA
BRAF HRAS PTEN
CDH1 IDH1 PTPN11
CSF1R JAK2 RB1
CTNNB1 JAK3 RET
EGFR KDR SMAD4
ERBB2 KIT SMARCB1
ERBB4 KRAS SMO
FBXW7 MET SRC
FGFR1 MLH1 STK11
FGFR2 MPL TP53
FGFR3 NOTCH1 VHL
FLT3    

Mutations tested by SNaPshotTM methodology:

IDH2 exon 4: 419G>A (R140Q), 419G>T (R140L), 514A>G (R172G), 514A>T (R172W), 515G>T (R172M), 515G>A (R172K), 515G>A (R172K)

DNM3TA exon 23: 2644C>T (R882C), 2644C>A (R882S), 2645G>A (R882H), 2645G>C (R882P)


 
 


 
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