Abstract
The effective differentiation between multiple primary lung tumors (MPs) and intrapulmonary metastases (IMs) in patients is imperative to discover the exact disease stage and to select the most appropriate treatment. In this study, the authors was to evaluate the efficacy and validity of large-scale targeted sequencing (LSTS) as a supplement to estimate whether multifocal lung cancers (MLCs) are primary or metastatic. Targeted sequencing of 520 cancer-related oncogenes was performed on 36 distinct tumors from 16 patients with MPs. Pairing analysis was performed to evaluate the somatic mutation pattern of MLCs in each patient. A total of 25 tumor pairs from 16 patients were sequenced, 88% (n = 22) of which were classified as MPs by LSTS, consistent with clinical diagnosis. One tumor pair from a patient with lymph node metastases had highly consistent somatic mutation profiles, thus predicted as a primary-metastatic pair. In addition, some matched mutations were observed in the remaining two paired ground-glass nodules (GGNs) and classified as high-probability IMs by LSTS. Our study revealed that LSTS can potentially facilitate the distinction of MPs from IMs. In addition, our results provide new genomic evidence of the presence of cancer invasion in GGNs, even pure GGNs.
Highlights
The effective differentiation between multiple primary lung tumors (MPs) and intrapulmonary metastases (IMs) in patients is imperative to discover the exact disease stage and to select the most appropriate treatment
These tumors were differentiated into sarcomatous carcinoma (SC, 2.8%) and adenocarcinomas (ADC, 97.2%), and the latter including adenocarcinoma in situ (AIS, 2.8%), minimal invasive adenocarcinoma (MIA, 11.1%) and invasive adenocarcinoma (IA, 83.3%) (Table 1)
In order to validate the clinical application of largescale targeted sequencing (LSTS) to distinguish MPs from IMs, the comprehensive mutational profiles of 25 tumor pairs were analyzed using a panel of 520 cancerrelated genes
Summary
The effective differentiation between multiple primary lung tumors (MPs) and intrapulmonary metastases (IMs) in patients is imperative to discover the exact disease stage and to select the most appropriate treatment. Targeted sequencing of 520 cancer-related oncogenes was performed on 36 distinct tumors from 16 patients with MPs. Pairing analysis was performed to evaluate the somatic mutation pattern of MLCs in each patient. A total of 25 tumor pairs from 16 patients were sequenced, 88% (n = 22) of which were classified as MPs by LSTS, consistent with clinical diagnosis. The identification of multiple primary lung tumors (MPs) and intrapulmonary metastases (IMs) is crucial in clinic practice, because IM is the malignant lung tumor in its advanced stage and a palliative treatment is generally adopted[3]. Mutational profiles were combined with clinical, radiological, and histopathological analysis to classify the paired tumors as MPs or IMs
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