Mutational status of synchronous and metachronous tumor samples in patients with metastatic non-small-cell lung cancer. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Quéré, Gilles; Descourt, Renaud; Robinet, Gilles; Autret, Sandrine; Raguenes, Odile; Fercot, Brigitte; Alemany, Pierre; Uguen, Arnaud; Férec, Claude; Quintin-Roué, Isabelle; Le Gac, Gérald
• Is Part Of: BMC cancer. Volume 16:Issue 1(2016)
• Page Start: 1
• Page End: 10
• Publication Date: 2016-12
• Subjects: Non-small-cell lung cancer -- Metastatic lesion -- Rebiopsy -- Genetic biomarkers -- Targeted therapy; Cancer -- Periodicals; 616.994005
• DOI: 10.1186/s12885-016-2249-6
• Languages: English
• ISSNs: 1471-2407

Abstract

Abstract Backgrounds Despite reported discordance between the mutational status of primary lung cancers and their metastases, metastatic sites are rarely biopsied and targeted therapy is guided by genetic biomarkers detected in the primary tumor. This situation is mostly explained by the apparent stability ofEGFR -activating mutations. Given the dramatic increase in the range of candidate drugs and high rates of drug resistance, rebiopsy or liquid biopsy may become widespread. The purpose of this study was to test genetic biomarkers used in clinical practice (EGFR, ALK ) and candidate biomarkers identified by the French National Cancer Institute (KRAS, BRAF, PIK3CA, HER2 ) in patients with metastatic non-small-cell lung cancer for whom two tumor samples were available. Methods A retrospective study identified 88 tumor samples collected synchronously or metachronously, from the same or two different sites, in 44 patients. Mutation analysis used SNaPshot (EGFR, KRAS, BRAF missense mutations), pyrosequencing (EGFR andPIK3CA missense mutations), sizing assays (EGFR andHER2 indels) and IHC and/or FISH (ALK rearrangements). Results About half the patients (52 %) harbored at least one mutation. Five patients had an activating mutation ofEGFR in both the primary tumor and the metastasis. The T790M resistance mutation was detected in metastases in 3 patients with acquired resistance toEGFR tyrosine kinase inhibitors. FISH showed discordance inALK status between a small biopsy sample and the surgical specimen.KRAS mutations were observed in 36 % of samples, six patients (14 %) having discordant genotypes; all discordances concerned sampling from different sites. Two patients (5 %) showedPI3KCA mutations. One metastasis harbored bothPI3KCA andKRAS mutations, while the synchronously sampled primary tumor was mutation free. No mutations were detected inBRAF andHER2 . Conclusions This study highlighted noteworthy intra-individual discordance inKRAS mutational status, whereasEGFR status was stable. Intratumoral heterogeneity forALK rearrangement suggests a limitation of single-biopsy analysis for therapeutic strategy with crizotinib.