Detection of activating EGFR and KRAS mutations in a single liquid biopsy from a patient with adenocarcinoma of the lung using hybrid capture based sequencing
23 February 2017 (online)
Liquid biopsies might uncover molecular clinically-relevant tumor heterogeneity, especially in the setting of resistance to therapy. Here we present a lung cancer patient, whose cell-free DNA (cfDNA) isolated from blood presented two mutually exclusive driver mutations, indicating the presence of two synchronous independent tumors in the lung.
At NEO New Oncology we have developed a hybrid-capture based next generation sequencing (NGS) assay called NEOliquid, capable of detecting genomic alterations, consisting of a panel of 39 cancer-related genes, in cfDNA of blood with high sensitivity and specificity.
Here we describe a 57-year-old female heavy smoker, diagnosed with adenocarcinoma of the lung with bone metastasis. Based on a previously identified EGFR Exon 19 deletion, the patient received Afatinib. Prior to therapy, peripheral blood from the patient was provided to NEO New Oncology, ctDNA was extracted and analysed using NEOliquid technology.
Molecular profiling of the liquid biopsy confirmed the EGFR Exon 19 deletion. Interestingly, additional alterations including an activating KRAS c.38G>A (p.G13D) mutation was detected, indicating the presence of a synchronous independent tumor.
Upon 8 weeks of Afatinib treatment, a marked reduction in the size of most tumor sites was observed, with the exception of the tumor in the right upper lobe. A mini-probe bronchioscopy confirmed the KRAS p.G13D alteration in the non-responding lesion, identical to the mutation previously detected in blood. In repeated liquid biopsies, following the course of Afatinib treatment, the KRAS mutation remained detectable, while the EGFR mutation disappeared.
To our knowledge, this is the first reported case of two synchronous lung tumors with different driver mutations, detected by a single liquid biopsy. Performing a liquid biopsy alongside standard tissue-based molecular diagnostics might be of benefit to allow for adjustment in cancer therapies.