Advance your NGS oncology fusion research

Extensive by design.

The Archer® FusionPlex® Oncology Research Kit is a targeted next generation sequencing (NGS) assay to simultaneously detect and identify fusions and other mutations associated with 75 genes found in RNA transcripts that are linked to various cancers. This kit is purpose-built to advance fusion discovery and extend the reach of precision medicine, including research efforts in the area of Ph-like ALL fusions.

Highlights

  • High throughput - Automation-ready protocol increases ability to systematically detect and discover fusions in tumor samples
  • Expert design - >98% panel uniformity and minimal off targeting due to superlatively optimized primer design. We've done the hard design work for you!
  • Extensive - the most comprehensive FusionPlex kit available

For Research Use Only. Not for use in diagnostic procedures.



Detecting Fusions Using the Archer FusionPlex Oncology Research Kit

ArcherDX has developed a comprehensive kit to rapidly detect translocations from total nucleic acid isolated from tumor samples, including FFPE preserved specimens. Anchored Multiplex PCR (AMP™) enrichment chemistry enables targeted amplification of fusion mRNAs, creating libraries that are optimal for multiplex NGS-based fusion detection. Archer technology permits the simultaneous detection of both known recurrent fusions as well as previously unidentified fusions at key breakpoints in target genes. The Archer FusionPlex Oncology Research Kit offers comprehensive NGS-based fusion detection, from library preparation through data analysis.


Ph-like Acute Lymphoblastic Leukemia

The FusionPlex Oncology Research Kit includes targets found in Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL), which is characterized by modifications in lymphoid transcription factor genes, poor outcomes, and a gene-expression profile similar to that of BCR-ABL1 ALL. Recent clinical and xenograft studies have revealed that the Ph-like ALL gene expression profile includes multiple genomic alterations, which are listed in the table below (table derived from [8]).

Kinase Fusions Identified in Ph-like Acute Lymphoblastic Leukemia

Kinase Gene Fusion Partners 5' Genes
ABL1 6 ETV6, NUP214, RCSD1, RANBP2, SNX2, ZMIZ1
ABL2 3 PAG1, RCSD1
CSF1R 1 SSBP2
PDGFRB 4 EBF1, SSBP2, TNIP1, ZEB2
CRLF2 2 P2RY8
JAK2 10 ATF7IP, BCR, ETV6, PAX5, PPFIBP1, SSBP2, STRN3, TERF2, TPR
EPOR* 2 IGH, IGK
IL2RB 1 MYH9
NTRK3 1 ETV6
PTK2B 2 KDM6A, STAG2
TSLP 1 IQGAP2
TYK2 1 MYB

*FusionPlex Oncology Research Kit will only detect an EPOR truncation


Precision Medicine

Precision medicine dramatically improves patient outcomes by applying highly-targeted therapies to individuals based on their genetic characterization. This forward-thinking approach to personalized care is enabled by advancements in medical technologies, including nucleic acid sequencing (first Sanger and more recently NGS), implementation of large-scale databases (e.g. the human genome), and bioinformatics tools to analyze and interpret data. While cancer is not the only area where precision medicine yields great gains in medical outcomes, it is the near-term focus.

Cancer is a disease of the genome, with each disease type characterized by unique molecular identifiers. Detection of these molecular biomarkers can lead to more accurate prognosis and treatment options for cancer sufferers. Furthermore, many targeted therapies have been, and will continue to be, developed with the aim of extending and improving quality of life. However, broad research programs like the one President Obama announced during his 2015 State of the Union Address are necessary to fully realize the dream of precision medicine.


Precision Medicine in Fusions

The landmark discovery that gene fusions drive the development of specific cancer subtypes empowered the development of a host of targeted therapies. The exclusivity of oncogenic fusion genes to cancer cells makes them attractive targets for such therapy. Furthermore, gene fusions are also used as diagnostic and prognostic biomarkers to confirm diagnosis and monitor clincial outcome in response to therapy, respectively. The advent of next-generation sequencing greatly expedited the discovery and characterization of gene fusions in a wide variety of cancer types.

Two of the most successful cancer drugs developed to date are crizotinib and imatinib. These drugs target specific tyrosine kinases that form chimeric fusions. Crizotinib is FDA approved for ALK positive fusions in NSCLC and Imatinib induces remission in leukemia patients that are positive for BCR-ABL fusions (6).

Discovery of fusions coincides with improved DNA sequencing technology

Figure 1. Gene fusion discovery coincides with the improvement of DNA sequencing technologies. Above the timeline, the colored boxes represent the year in which the denoted gene fusion was discovered, while arrows below the timeline represent the year in which certain DNA sequencing technologies became available (graphic derived from [7]). The acronyms below the gene fusions represent the type of cancer with which it is associated:

  • ACC - adenoid cystic carcinoma
  • ALCL - anaplastic large cell lymphoma
  • ALL - acute lymphocytic leukemia
  • AML - acute myeloid leukemia
  • APL - acute promyelocytic leukemia
  • BC - bladder cancer
  • BL - Burkitt lymphoma
  • CF - congenital fibrosarcoma
  • CML - chronic myelogenous leukemia
  • CRC - colorectal cancer
  • ES - Ewing sarcoma
  • FTC - follicular thyroid carcinoma
  • GBM - glioblastoma multiforma
  • IMT - inflammatory myofibroblastic tumor
  • MC - mucoepidermoid carcinoma
  • ML - myxoid liposarcoma
  • NMC - nut midline carcinoma
  • NSCLC - non-small cell lung cancer
  • PA - pilocytic astrocytoma
  • PC - prostate cancer
  • PRCC - pediatric renal cell carcinoma
  • SBC - secretory breast carcinoma
  • SOC - serious ovarian cancer
  • SS - synovial sarcoma

FusionPlex Oncology Research Kit Targets


Gene Accession Target Exons Direction Assay Type
ABL1 NM_005157.4 2,3,4 5 Fusion
ABL2 NM_007314 4,5,6 5 Fusion
AKT1 NM_005163 2,3,5 5 Fusion
AKT2 NM_001626 5 5 Fusion
AKT3 NM_005465 1,2,3 5 Fusion
ALK NM_004304 Intron 19 5 Fusion
ALK NM_004304 2,17,19,20,21,22 5 Fusion
ARHGAP26 NM_015071 2,10,11,12 5 Fusion
AXL NM_021913 19,20 3 Fusions
BRAF NM_004333 7,8 3 Fusion
BRAF NM_004333 7,8,9,10,11,12 5 Fusion
BRAF NM_004333 15 5 SNP (V600E)
BRD3 NM_007371 9,10,11,12 3 Fusion
BRD4 NM_058243 10,11 3 Fusion
CRLF2 NM_022148 1 5 Fusion
CSF1R NM_005211 11,12,13 5 Fusion
EGFR NM_005228 7,8,9,16,20 5 Fusion
EGFR NM_005228 24,25 3 Fusion
EPOR NM_000121 1,2 5 Fusion
EPOR NM_000121 7,8 3 Truncation
ERBB2 NM_001005862 2,3,4,5,6,7,8,9,10,11,12,13,14,15,17,18 5 Fusion
ERBB4 NM_005235 2,3,4 3 Fusion
ERG NM_004449 2,3,4,5,6,7,8,9,10,11 5 Fusion
ESR1 NM_001122742 1,2,3,4,5,6 3 Fusion
ESRRA NM_0044514 2,3 3 Fusion
ETV1 NM_004956 3,4,5,6,7,8,9,10,11,12,13 5 Fusion
ETV4 NM_001986 2,4,5,6,7,8,9,10 5 Fusion
ETV5 NM_004454 2,3,7,8,9 5 Fusion
ETV6 NM_001987 1,2,3,4,5,6 3 Fusion
ETV6 NM_001987 2,3,5,6,7 5 Fusion
EWSR1 NM_005243 4,5,6,7,8,9,10,11,12,13,14 3 Fusion
FGFR1 NM_015850 2,8,9,10 5 Fusion
FGFR1 NM_015850 17 3 Fusion
FGFR2 NM_000141.4 2,8,9,10 5 Fusion
FGFR2 NM_000141.4 17 3 Fusion
FGFR3 NM_000142 Intron 18 3 Fusion
FGFR3 NM_000142 8,9,10 5 Fusion
FGFR3 NM_000142 17 3 Fusion
FGR NM_005248 2 5 Fusion
IL2RB NM_000878.3 2 5 Fusion
INSR NM_000208 12,13,14,15,16,18,19 5 Fusion
INSR NM_000208 20,21,22 3 Fusion
JAK1 NM_002227 9,11,16,17,19 5 Fusion
JAK1 NM_002227 9,11,16,17,19 3 Fusion
JAK2 NM_004972 9,10,11,12,13,14,16,17,18,19 5 Fusion
JAK3 NM_000215 9,10,11,12,13,14,15,16,17,18,19 5 Fusion
KIT NM_000222 11 5 Fusion
MAML2 NM_032427 2,3 5 Fusion
MAST1 NM_014975 7,8,9,18,19,20,21 5 Fusion
MAST2 NM_015112.2 2,3,5,6 5 Fusion
MET NM_000245 2,13,14,15,16 5 Fusion
MET NM_000245 13,15 (exon 14 skipping event) N/A Mutation
MSMB NM_002443 2,3,4 3 Fusion
MUSK NM_005592 7,8,9,11,12,13,14 5 Fusion
MYB NM_001130173 7,8,9,11,12,13,14,15,16 3 Fusion
MYC NM_002467 1,2,3 5 Fusion
MYC NM_002467 3 3 Fusion
NOTCH1 NM_017617.3 26,27,28,29 (internal deletion exons 3-27) 5 Fusion
NOTCH1 NM_017617.3 2,4,29,30,31 3 Fusion
NOTCH2 NM_024408 5,6,7 3 Fusion
NOTCH2 NM_024408 26,27,28 5 Fusion
NRG1 NM_004495 1,2,3,6 5 Fusion
NTRK1 NM_002529 8,10,11,12,13 5 Fusion
NTRK2 NM_006180 11,12,13,14,15,16,17 5 Fusion
NTRK3 NM_002530 13,144,15,16 5 Fusion
NTRK3 NM_001007156 15 5 Fusion
NUMBL NM_004756 3 5 Fusion
NUT NM_175741 3 5 Fusion
PDGFRA NM_006206 7 (exon 8 deletion) 3 Deletion
PDGFRA NM_006206 10,11,12,13,14,15,18 5 Fusion
PDGFRA NM_006206 T6741iv,D842v N/A Mutation
PDGFRB NM_002609 8,9,10,11,12,13,14 5 Fusion
PIK3CA NM_006218 2 5 Fusion
PKN1 NM_002741 10,11,12,13 5 Fusion
PPARG NM_015869 1,2,3,4 5 Fusion
PRKCA NM_002737.2 4,5,6 5 Fusion
PRKCB NM_002738 3 5 Fusion
PTK2B NM_173174 6,7,8 5 Fusion
RAF1 NM_002880 4,5,6,7,9,10,11,12 3 Fusion
RAF1 NM_002880 4,5,6,7,9,10,11,12 5 Fusion
RARA NM_000964 2,3,4 5 Fusion
RARA NM_000964 3 3 Fusion
RELA NM_021975.3 3,4 5 Fusion
RET NM_020975.4 8,9,10,11,12,13 5 Fusion
ROS1 NM_002944.2 31,32,33,34,35,36,37 5 Fusion
RSPO2 NM_178565.4 1,2 5 Fusion
RSPO3 NM_032784.4 2 5 Fusion
SYK NM_003177 5 5 Fusion
TERT NM_198253 2 5 Fusion
TFE3 NM_006521 2,3,4,5,6,7,8 5 Fusion
TFE3 NM_006521 2,3,4,5,6 3 Fusion
TFEB NM_007162.2 1,2 5 Fusion
THADA NM_022065 24,25,26,27,28,29,30 3 Fusion
TMPRSS2 NM_005656 1 3 Fusion
TMPRSS2 NM_001135099 1,2,3,4,5,6 3 Fusion
TSLP NM_033035.4 1 5 Fusion
TYK2 NM_003331.4 18 5 Fusion

Resources

  1. Cantwell-Dorris et al. BRAFV600E: Implications for Carcinogenesis and Molecular Therapy. MOL Cancer Ther. 10(3):385-94(2011)
  2. Ma et al. c-MET mutational analysis in small cell lung cancer: novel juxtamembrane domain mutations regulating cytoskeletal functions. Cancer Res. 63(19):6272-81 (2003).
  3. Ashworth et al. Deletion-based mechanisms of NOTCH1 activation in T-ALL: key roles for RAG recombinase and a conserved internal translational start site in NOTCH1. Blood. 116(25):5455-5464 (2010).
  4. Ozawa et al. PDGFRA gene rearrangements are frequent genetic events in PDGFRA-amplified glioblastomas. Genes & Dev. 24: 2205-2218 (2010).
  5. E. Lierman et al., FIP1L1-PDGFRalpha D842V, a novel panresistant mutant, emerging after treatment of FIP1L1-PDGFRalpha T674I eosinophilic leukemia with single agent sorafenib. Leukemia. 23:845-851 (2009).
  6. 1. S. E. Jackson, J. D. Chester, Personalised cancer medicine. Int. J. Cancer. 137, 262–266 (2015).
  7. M. J. Annala, B. C. Parker, W. Zhang, M. Nykter, Fusion genes and their discovery using high throughput sequencing. Cancer Lett. 340, 192–200 (2013).
  8. K. G. Roberts et al., Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. N. Engl. J. Med. 371, 1005–1015 (2014).

How to contact us

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Phone

Phone: (877) 771 1093

Phone: (303) 357 9001

All content © 2017 ArcherDX, Inc.

For Research Use Only. Not for use in diagnostic procedures. For Research Use Only. Not for use in diagnostic procedures.