Support

Publications

Search through our support documentation and FAQs for ArcherDX, now Invitae, products and services.

Invitae technology is featured in >365 posters and peer reviewed publications.

Featured Publications

Chang F1, Lin F2, Cao K2, Surrey LF1, Aplenc R3, Bagatell R3, Resnick AC4, Santi M1, Storm PB3, Tasian SK3, Waanders AJ3, Hunger SP3, Li MM5.

Author Information

  1. Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
  2. Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania.
  3. Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania.
  4. Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; Department of Biomedical and Health Informatics, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania.
  5. Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania. Electronic address: [email protected]

Gene fusions are one of the most common genomic alterations in pediatric cancer. Many fusions encode oncogenic drivers and play important roles in cancer diagnosis, risk stratification, and treatment selection. We report the development and clinical validation of a large custom-designed RNA sequencing panel, CHOP Fusion panel, using anchored multiplex PCR technology. The panel interrogates 106 cancer genes known to be involved in nearly 600 different fusions reported in hematological malignancies and solid tumors. The panel works well with different types of samples, including formalin-fixed, paraffin-embedded samples. The panel demonstrated excellent analytic accuracy, with 100% sensitivity and specificity on 60 pediatric tumor validation samples. In addition to identifying all known fusions in the validation samples, three unrecognized, yet clinically significant, fusions were also detected. A total of 276 clinical cases were analyzed after the validation, and 51 different fusions were identified in 104 cases. Of these fusions, 16 were not previously reported at the time of discovery. These fusions provided genomic information useful for clinical management. Our experience demonstrates that CHOP Fusion panel can detect the vast majority of known and certain novel clinically relevant fusion genes in pediatric cancers accurately, efficiently, and cost-effectively; and the panel provides an excellent tool for new fusion gene discovery.

Copyright © 2019 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Benayed R1, Offin M2, Mullaney K1, Sukhadia P1, Rios K1, Desmeules P3, Ptashkin R1, Won H4, Chang J1, Halpenny D5, Schram AM6, Rudin CM2,6,7, Hyman DM6, Arcila ME1, Berger MF1, Zehir A1, Kris MG2,6,7, Drilon A2,6,7, Ladanyi M8.

Author Information

  1. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
  2. Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
  3. Department of Pathology, Quebec Heart and Lung Institute, Quebec City, Quebec, Canada.
  4. Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
  5. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.
  6. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
  7. Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, New York.
  8. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York. [email protected]

PURPOSE:
Targeted next-generation sequencing of DNA has become more widely used in the management of patients with lung adenocarcinoma; however, no clear mitogenic driver alteration is found in some cases. We evaluated the incremental benefit of targeted RNA sequencing (RNAseq) in the identification of gene fusions and MET exon 14 (METex14) alterations in DNA sequencing (DNAseq) driver-negative lung cancers.

EXPERIMENTAL DESIGN:
Lung cancers driver negative by MSK-IMPACT underwent further analysis using a custom RNAseq panel (MSK-Fusion). Tumor mutation burden (TMB) was assessed as a potential prioritization criterion for targeted RNAseq.

RESULTS:
As part of prospective clinical genomic testing, we profiled 2,522 lung adenocarcinomas using MSK-IMPACT, which identified 195 (7.7%) fusions and 119 (4.7%) METex14 alterations. Among 275 driver-negative cases with available tissue, 254 (92%) had sufficient material for RNAseq. A previously undetected alteration was identified in 14% (36/254) of cases, 33 of which were actionable (27 in-frame fusions, 6 METex14). Of these 33 patients, 10 then received matched targeted therapy, which achieved clinical benefit in 8 (80%). In the 32% (81/254) of DNAseq driver-negative cases with low TMB [0-5 mutations/Megabase (mut/Mb)], 25 (31%) were positive for previously undetected gene fusions on RNAseq, whereas, in 151 cases with TMB >5 mut/Mb, only 7% were positive for fusions (P < 0.0001).

CONCLUSIONS:
Targeted RNAseq assays should be used in all cases that appear driver negative by DNAseq assays to ensure comprehensive detection of actionable gene rearrangements. Furthermore, we observed a significant enrichment for fusions in DNAseq driver-negative samples with low TMB, supporting the prioritization of such cases for additional RNAseq.See related commentary by Davies and Aisner, p. 4586.

©2019 American Association for Cancer Research.

Afrin S1, Zhang CRC1, Meyer C2, Stinson CL1, Pham T1, Bruxner TJC3, Venn NC4, Trahair TN5, Sutton R4, Marschalek R2, Fink JL#1, Moore AS#6,7,8. Author Information
  1. The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia.
  2. Institute of Pharm. Biology/DCAL, Goethe-University, Frankfurt/Main, Germany.
  3. Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
  4. Children’s Cancer Institute, University of New South Wales, Sydney, Australia.
  5. Kids Cancer Centre, Sydney Children’s Hospital, Sydney, Australia.
  6. The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia. [email protected]
  7. Oncology Services Group, Children’s Health Queensland Hospital and Health Service, Brisbane, Australia.
  8. UQ Child Health Research Centre, The University of Queensland, Brisbane, Australia.#Contributed equally

Mixed lineage leukemia (MLLgene rearrangements characterize approximately 70% of infant and 10% of adult and therapy-related leukemia. Conventional clinical diagnostics, including cytogenetics and fluorescence in situ hybridization (FISH) fail to detect MLL translocation partner genes (TPG) in many patients. Long-distance inverse (LDI)-PCR, the “gold standard” technique that is used to characterize MLL breakpoints, is laborious and requires a large input of genomic DNA (gDNA). To overcome the limitations of current techniques, a targeted next-generation sequencing (NGS) approach that requires low RNA input was tested. Anchored multiplex PCR-based enrichment (AMP-E) was used to rapidly identify a broad range of MLL fusions in patient specimens. Libraries generated using FusionPlex® Heme and Myeloid panels were sequenced using the Illumina platform. Diagnostic specimens (n = 39) from pediatric leukemia patients were tested with AMP-E and validated by LDI-PCR. In concordance with LDI-PCR, the AMP-E method successfully identified TPGs without prior knowledge. AMP-E identified 10 different MLL fusions in the 39 samples. Only two specimens were discordant; AMP-E successfully identified a MLL-MLLT1 fusion where LDI-PCR had failed to determine the breakpoint, whereas a MLL-MLLT3 fusion was not detected by AMP-E due to low expression of the fusion transcript. Sensitivity assays demonstrated that AMP-E can detect MLL-AFF1 in MV4-11 cell dilutions of 10-7 and transcripts down to 0.005 copies/ng. Implications: This study demonstrates a NGS methodology with improved sensitivity compared with current diagnostic methods for MLL-rearranged leukemia. Furthermore, this assay rapidly and reliably identifies MLL partner genes and patient-specific fusion sequences that could be used for monitoring minimal residual disease. Mol Cancer Res; 16(2); 279-85. ©2017 AACR.

Schalper KA1, Rodriguez-Ruiz ME2,3,4, Diez-Valle R5,6, López-Janeiro A7, Porciuncula A1, Idoate MA7, Inogés S6, de Andrea C7, López-Diaz de Cerio A6, Tejada S5, Berraondo P8, Villarroel-Espindola F1, Choi J9, Gúrpide A2, Giraldez M10, Goicoechea I2, Gallego Perez-Larraya J11, Sanmamed MF1,2, Perez-Gracia JL2,3,4, Melero I12,13,14,15. Author Information
  1. Department of Pathology, Yale School of Medicine, New Haven, CT, USA.
  2. Department of Oncology, Clínica Universidad de Navarra, Pamplona, Spain.
  3. Centro de Investigación Biomedica en Red de Oncología (CIBERONC), Madrid, Spain.
  4. Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Spain.
  5. Department of Neurosurgery, Clínica Universidad de Navarra, Pamplona, Spain.
  6. Department of Immunology, Clínica Universidad de Navarra, Pamplona, Spain.
  7. Department of Pathology, Clínica Universidad de Navarra, Pamplona, Spain.
  8. Centro de Investigación Medica Aplicada (CIMA), Universidad de Navarra, Pamplona, Spain.
  9. Department of Genetics, Yale School of Medicine, New Haven, CT, USA.
  10. Department of Pharmacy, Clínica Universidad de Navarra, Pamplona, Spain.
  11. Department of Neurology, Clínica Universidad de Navarra, Pamplona, Spain.
  12. Centro de Investigación Biomedica en Red de Oncología (CIBERONC), Madrid, Spain. [email protected]
  13. Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Spain. [email protected]
  14. Department of Neurosurgery, Clínica Universidad de Navarra, Pamplona, Spain. [email protected]
  15. Department of Immunology, Clínica Universidad de Navarra, Pamplona, Spain. [email protected]

Glioblastoma is the most common primary central nervous system malignancy and has a poor prognosis. Standard first-line treatment, which includes surgery followed by adjuvant radio-chemotherapy, produces only modest benefits to survival1,2. Here, to explore the feasibility, safety and immunobiological effects of PD-1 blockade in patients undergoing surgery for glioblastoma, we conducted a single-arm phase II clinical trial (NCT02550249) in which we tested a presurgical dose of nivolumab followed by postsurgical nivolumab until disease progression or unacceptable toxicity in 30 patients (27 salvage surgeries for recurrent cases and 3 cases of primary surgery for newly diagnosed patients). Availability of tumor tissue pre- and post-nivolumab dosing and from additional patients who did not receive nivolumab allowed the evaluation of changes in the tumor immune microenvironment using multiple molecular and cellular analyses. Neoadjuvant nivolumab resulted in enhanced expression of chemokine transcripts, higher immune cell infiltration and augmented TCR clonal diversity among tumor-infiltrating T lymphocytes, supporting a local immunomodulatory effect of treatment. Although no obvious clinical benefit was substantiated following salvage surgery, two of the three patients treated with nivolumab before and after primary surgery remain alive 33 and 28 months later.

You are now leaving support.archerdx.com. Links to sites outside of ArcherDX or Invitae are provided as a resource to the viewer. Invitae accepts no responsibility for the content of linked sites.

You are now leaving archerdx.com. Links to sites outside of ArcherDX are provided as a resource to the viewer. ArcherDX accepts no responsibility for the content of linked sites. 

You are now leaving archerdx.com. Links to sites outside of ArcherDX are provided as a resource to the viewer. ArcherDX accepts no responsibility for the content of linked sites. 

You are now leaving archerdx.com. Links to sites outside of ArcherDX are provided as a resource to the viewer. ArcherDX accepts no responsibility for the content of linked sites. 

This website stores cookies on your computer. These cookies are used to improve your website and provide more personalized services to you, both on this website and through other media. To find out more about the cookies we use, see our Privacy Policy.

We won’t track your information when you visit our site. But in order to comply with your preferences, we’ll have to use just one tiny cookie so that you’re not asked to make this choice again.