Utility of genomic analysis in circulating tumor DNA from patients with carcinoma of unknown primary.

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Utility of genomic analysis in circulating tumor DNA from patients with carcinoma of unknown primary.

Cancer Res. 2017 Jun 22;:

Authors: Kato S, Krishnamurthy N, Banks KC, De P, Williams K, Williams C, Leyland-Jones B, Lippman SM, Lanman RB, Kurzrock R

Abstract
Carcinoma of unknown primary (CUP) is a rare and difficult-to-treat malignancy, the management of which might be improved by the identification of actionable driver mutations. We interrogated interrogated 54-70 genes in 442 patients with CUP using targeted clinical-grade, next-generation sequencing (NGS) of circulating tumor DNA (ctDNA). Overall, 80% of patients exhibited ctDNA alterations; 66%, ≥ 1 characterized alteration(s) excluding variants of unknown significance. TP53-associated genes were most commonly altered (37.8%) followed by genes involved in the MAPK pathway (31.2%), PI3K signaling (18.1%) and the cell cycle machinery (10.4%). Distinct genomic profiles were observed in 87.9% of CUP cases with 99.7% exhibiting potentially targetable alterations. An illustrative patient with dynamic changes in ctDNA content during therapy and a responder given a checkpoint inhibitor-based regimen because of a mismatch repair gene anomaly are presented. Our results demonstrate that ctDNA evaluation is feasible in CUP and that most patients harbor a unique somatic profile with pharmacologically actionable alterations, justifying the inclusion of non-invasive liquid biopsies in next-generation clinical trials.

PMID: 28642281 [PubMed - as supplied by publisher]

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