Yale Cancer Center Precision Medicine Tumor Board: new technology, new drugs, and the value of repeat testing

• Published in: The lancet oncology 2020-03, Vol.21 (3), p.343-344
• Main Authors: Hafez, Navid, Walther, Zenta, Eder, Joseph P, Sklar, Jeffrey L, Gettinger, Scott N, Finberg, Karin E, Goldberg, Sarah B
• Format: Article
• Language: English
• Subjects: Cancer therapies; Clinical trials; Deoxyribonucleic acid; DNA; FDA approval; Gene fusion; Genes; Immunotherapy; Kinases; Laboratories; Lung cancer; Lymphatic system; Monoclonal antibodies; Mutation; Papillary thyroid cancer; Pathology; Patients; Pembrolizumab; Polymerase chain reaction; Precision medicine; Protein-tyrosine kinase; Ret protein; Ribonucleic acid; RNA; Signal transduction; Targeted cancer therapy; Thyroid cancer; Thyroid carcinoma; Tumors
• ISSN: 1470-2045; 1474-5488
• DOI: 10.1016/S1470-2045(20)30010-3

RET status was not evaluable due to technical failure of the assay. Since no driver alteration was detected, the patient was treated with pembrolizumab as part of a clinical trial and had prolonged disease stability. Oncogenic activation of the RET tyrosine kinase can occur via mutation of the coding sequence (often found in medullary thyroid carcinoma), or by chromosomal rearrangement that fuses the kinase domain of RET to a variety of partner genes (often found in papillary thyroid cancer). Others assays, such as the Oncomine assay, identify gene fusions in the tumour RNA by sequencing the products of a multiplex RT-PCR reaction designed to amplify specific fusion junctions among transcripts generated by a large set of possible gene fusions. Because oncogenic gene fusions are expected to be highly expressed, RNA-based methods might have greater sensitivity to detect gene fusion events compared with DNA-based methods in samples with low malignant cell content.