In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 22_Supplement_1 ( 2015-11-15), p. A1-43-A1-43
Kurzfassung:
Background: Although precision medicine approaches have revolutionized oncology, widespread adoption requires robust, inexpensive approaches enabling the targeted assessment of all relevant alteration classes from routine tissue samples. Methods: Here we interrogated & gt;7,000 cancer exomes and transcriptomes, along with & gt;30,000 array based cancer genomes to identify recurrent somatic alterations (mutations, copy number alterations [CNAs] and gene fusions) across solid tumors. From this analysis, we developed and validated an integrated multiplexed PCR based Ion Torrent next generation sequencing panel (Oncomine Cancer Research Panel [OCP] ) targeting the actionable somatic cancer genome optimized for 20ng of formalin-fixed, paraffin-embedded (FFPE) tissue isolated DNA/RNA. Results: We validated the OCP using FFPE cell line mixtures, as well as a prospective cohort of 104 FFPE tumor specimens sent for concurrent clinical molecular testing, with & gt;97% sensitivity and specificity for the presence/absence of KRAS, EGFR, BRAF and ALK point mutations, indels or gene fusions in this molecular testing cohort. We also applied the OCP to 100 lung cancers, identifying known and novel alterations, including ALK and ROS1 gene fusions. Lastly, applying the OCP to 116 prostate cancers, including 50 previously treated samples, we recapitulated known molecular subtypes, observed distinct profiles according to previous treatment and obtained 100% concordance for isoform specific TMPRSS2:ERG gene fusion detection compared to qPCR. Additionally, OCP profiling supports a novel molecular subtype of prostate cancer defined by IDH1 R132 hotspot mutations and informed on resistance mechanisms in a pre- and post-treatment sample pair. Importantly, 44%, 35% and 9% of patients in the molecular testing, lung and prostate cancer cohorts, respectively, harbored additional alterations (beyond routine molecular testing) associated with FDA approved or NCCN guideline referenced therapies. Conclusions: Through analysis of both DNA and RNA to assess the actionable somatic cancer genome, the validated OCP panel may have utility in both clinical and research settings. Citation Format: Daniel H. Hovelson, Andrew S. McDaniel, Bryan Johnson, Andi K. Cani, Kate Rhodes, Paul D. Williams, Chia-Jen Liu, Santhoshi Bandla, Catherine S. Grasso, Michael J. Quist, Seth Sadis, Daniel R. Rhodes, Scott A. Tomlins. Targeted amplicon-based next-generation sequencing of routine solid tumor specimens to detect clinically relevant somatic alterations. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A1-43.
Materialart:
Online-Ressource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.TRANSCAGEN-A1-43
Sprache:
Englisch
Verlag:
American Association for Cancer Research (AACR)
Publikationsdatum:
2015
ZDB Id:
2036785-5
ZDB Id:
1432-1
ZDB Id:
410466-3
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