Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Translational research

4039 - Co-amplification of KIT/KDR/PDGRA in over 100,000 advanced cancer cases

Date

09 Sep 2017

Session

Translational research

Presenters

umut Disel

Citation

Annals of Oncology (2017) 28 (suppl_5): v573-v594. 10.1093/annonc/mdx390

Authors

U. Disel1, R. Madison2, J. Chung3, M. Gounder4, A. Oztan5, A. Benson6, J. Webster6, S.J. Klempner7, S.I. Ou8, S. Ganesan9, K. Janeway10, P.J. Stephens2, J.S. Ross11, A.B. Schrock3, V.A. Miller12, S. Ali3

Author affiliations

  • 1 Medical Oncology, Adana Numune Education and Research Hospital, 0000 - Adana/TR
  • 2 R & D, Foundation Medicine, 02141 - Cambridge/US
  • 3 Clinical Development, Foundation Medicine, MA 02141 - Cambridge/US
  • 4 Sarcoma Oncoogy, memorial sloan kettering cancer center, 10065 - new york/US
  • 5 Biomedical Informatics, Foundation Medicine, MA 02141 - Cambridge/US
  • 6 Clinical Operations, Foundation Medicine, MA 02141 - Cambridge/US
  • 7 Medical Oncology, The Angeles Clinic and Research Institute, 90025 - Los Angeles/US
  • 8 Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, 92868 - Orange/US
  • 9 Cancer Institute Of New Jersey, rutgers university, 08903 - new brunswick/US
  • 10 Pediatric Oncology, Dana Farber Cancer Institute, 02115 - boston/US
  • 11 Pathology, Albany Medical Center, 12208 - Albany/US
  • 12 Medical Group, Foundation Medicine, MA 02141 - Cambridge/US
More

Resources

Abstract 4039

Background

The 4q12 amplicon (4q12amp) which harbors the tyrosine kinases KIT, KDR and PDGFRA has been thought to occur as frequently as 3-7% in lung adenocarcinoma (LA) (Ramos et al, 2009) and 5-15% in glioblastoma (GBM) (Holtkamp, 2006; Szerlip, 2012) as assessed by a variety of techniques. As 4q12amp is hypothesized to be an oncogenic driver, it remains unclear whether all three kinases participate equally in oncogenesis, or if one kinase can be preferentially targeted by a tyrosine kinase inhibitor (TKI) for patient benefit. We undertook a large-scale genomic analysis to describe the frequency of 4q12 across solid tumors.

Methods

We prospectively analyzed 114,200 primarily advanced stage solid tumors in the course of clinical care using hybrid-capture based comprehensive genomic profiling (CGP) of 186 to 315 genes plus introns from 14 to 28 genes commonly rearranged in cancer.

Results

4q12amp was present in 0.65% of all cases (740/114,200), with a median copy number of 10, and was most abundant in the following cancers: 4.8% of GBM (155/3,222), 0.83% of lung cancers (191/22,857, 2/3 approximately being LA), 1.9% of sarcomas (106/5,391), and 0.77% of breast cancers (92/11,980). Of sarcomas, 7.1% of osteosarcomas (26/367) and 2.82% of soft tissue sarcomas NOS (22/780) harbored 4q12amp. Of 4q12amp lung cancer cases, the supramajority (86%) did not harbor known oncogenic drivers of NSCLC (alterations of EGFR/HER2/MET, ALK/ROS/RET fusions, or BRAF V600E). Index cases of durable responses to pazopanib and imatinib will be described in undifferentiated sarcoma, synovial sarcoma, and head and neck/salivary cancers.

Conclusions

4q12amp is significantly less frequent in GBM and lung cancer than previously reported by non-sequencing techniques, but is enriched in osteosarcoma and undifferentiated sarcomas. The driver status of 4q12amp is supported both by the predominant mutual exclusivity with other known drivers in lung cancer, and responses to various multi-TKIs. The specificities of the latter may help shed insight into whether singly or multiply targeting KIT/KDR/PDGFRA is a preferred approach for patient benefit.

Clinical trial identification

Legal entity responsible for the study

Foundation Medicine

Funding

Foundation medicine, Inc funded a small part of the study

Disclosure

U. Disel: Research agreement with Foundation Medicine, which provided funding to run a small number of genomic profiling assay (

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.